Pyridone gpr119 g protein-coupled receptor agonists

ABSTRACT

Novel compounds are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. These novel compounds have the structure Formula I or Formula IA.

RELATED APPLICATION

This application is a divisional application of U.S. patent applicationSer. No. 13/159,497, filed Jun. 14, 2011, now allowed, which claimspriority benefit of U.S. patent application Ser. No. 12/173,856, filedon Jul. 16, 2008, issued as U.S. Pat. No. 8,003,796 B2, which claimspriority benefit of U.S. Provisional Application No. 60/950,162, filedon Jul. 17, 2007. The entirety of each of these applications isincorporated herein by reference.

BACKGROUND OF THE INVENTION

Diabetes mellitus is a serious disease afflicting over 100 millionpeople worldwide. In the United States, there are more than 12 milliondiabetics, with 600,000 new cases diagnosed each year. Diabetes mellitusis a diagnostic term for a group of disorders characterized by abnormalglucose homeostasis resulting in elevated blood sugar. There are manytypes of diabetes, but the two most common are Type 1 (also referred toas insulin-dependent diabetes mellitus or IDDM) and Type 2 (alsoreferred to as non-insulin-dependent diabetes mellitus or NIDDM).

The etiology of the different types of diabetes is not the same;however, everyone with diabetes has two things in common: overproductionof glucose by the liver and little or no ability to move glucose out ofthe blood into the cells where it becomes the body's primary fuel.

People who do not have diabetes rely on insulin, a hormone made in thepancreas, to move glucose from the blood into the cells of the body.However, people who have diabetes either do not produce insulin orcannot efficiently use the insulin they produce; therefore, they cannotmove glucose into their cells. Glucose accumulates in the blood creatinga condition called hyperglycemia, and over time, can cause serioushealth problems.

Diabetes is a syndrome with interrelated metabolic, vascular, andneuropathic components. The metabolic syndrome, generally characterizedby hyperglycemia, comprises alterations in carbohydrate, fat and proteinmetabolism caused by absent or markedly reduced insulin secretion and/orineffective insulin action. The vascular syndrome consists ofabnormalities in the blood vessels leading to cardiovascular, retinaland renal complications. Abnormalities in the peripheral and autonomicnervous systems are also part of the diabetic syndrome.

Diabetes has also been implicated in the development of kidney disease,eye diseases and nervous-system problems. Kidney disease, also callednephropathy, occurs when the kidney's “filter mechanism” is damaged andprotein leaks into urine in excessive amounts and eventually the kidneyfails. Diabetes is also a leading cause of damage to the retina at theback of the eye and increases risk of cataracts and glaucoma. Finally,diabetes is associated with nerve damage, especially in the legs andfeet, which interferes with the ability to sense pain and contributes toserious infections. Taken together, diabetes complications are one ofthe nation's leading causes of death.

Many people with NIDDM have sedentary lifestyles and are obese; theyweigh approximately 20% more than the recommended weight for theirheight and build. Furthermore, obesity is characterized byhyperinsulinemia and insulin resistance, a feature shared with NIDDM,hypertension and atherosclerosis.

Obesity, which is the result of an imbalance between caloric intake andenergy expenditure, is highly correlated with insulin resistance anddiabetes in experimental animals and human. However, the molecularmechanisms that are involved in obesity-diabetes syndromes are notclear. During early development of obesity, increased insulin secretionbalances insulin resistance and protects patients from hyperglycemia (LeStunff et al., Diabetes, 43:696-702 (1989)). However, over time, β-cellfunction deteriorates and non-insulin-dependent diabetes develops inabout 20% of the obese population (Pederson, P., Diab. Metab. Rev.,5:505-509 (1989)) and (Brancati, F. L. et al., Arch. Intern. Med.,159:957-963 (1999)). Given its high prevalence in modern societies,obesity has thus become the leading risk factor for NIDDM (Hill, J. O.et al., Science, 280:1371-1374 (1998)). However, the factors whichpredispose a fraction of patients to alteration of insulin secretion inresponse to fat accumulation remain unknown. The most common diseaseswith obesity are cardiovascular disease (particularly hypertension),diabetes (obesity aggravates the development of diabetes), gall bladderdisease (particularly cancer) and diseases of reproduction. Research hasshown that even a modest reduction in body weight can correspond to asignificant reduction in the risk of developing coronary heart disease.

Obesity considerably increases the risk of developing cardiovasculardiseases as well. Coronary insufficiency, atheromatous disease, andcardiac insufficiency are at the forefront of the cardiovascularcomplication induced by obesity. It is estimated that if the entirepopulation had an ideal weight, the risk of coronary insufficiency woulddecrease by 25% and the risk of cardiac insufficiency and of cerebralvascular accidents by 35%. The incidence of coronary diseases is doubledin subjects less than 50 years of age who are 30% overweight. Thediabetes patient faces a 30% reduced lifespan. After age 45, people withdiabetes are about three times more likely than people without diabetesto have significant heart disease and up to five times more likely tohave a stroke. These findings emphasize the inter-relations betweenrisks factors for NIDDM, obesity and coronary heart disease as well asthe potential value of an integrated approach involving the treatment ofboth obesity and diabetes (Perry, I. J. et al., BMJ, 310:560-564(1995)).

Type 2 diabetes results from the progressive loss of pancreatic β-cellfunction in the presence of insulin resistance, leading to an overallreduction in insulin output (Prentki, M. et al., “Islet failure in type2 diabetes”, J. Clin. Invest., 116:1802-1812 (2006)). β-cells are thecell type that store and release insulin in response to an elevation inplasma glucose or in response to hormonal signals from the gut followingthe ingestion of food. Evidence suggests that in type 2 diabetics therate of β-cell cell death (apoptosis) exceeds that of new β-celldevelopment, yielding an overall loss in β-cell number (Butler, A. E. etal., “β-cell deficit and increased β-cell apoptosis in humans with type2 diabetes”, Diabetes, 52:102-110 (2003)). β-cell apoptosis may arisefrom persistent elevations in plasma glucose levels (glucotoxicity)and/or plasma lipid levels (lipotoxicity).

G-protein coupled receptors (GPCRs) expressed on β-cells are known tomodulate the release of insulin in response to changes in plasma glucoselevels (Ahren, B., “Autonomic regulation of islet hormonesecretion—Implications for health and disease”, Diabetologia, 43:393-410(2003)). Those GPCRs specifically coupled to the elevation of cAMP viathe G_(s) alpha subunit of G-protein, have been shown to enhanceglucose-stimulated insulin release from β-cells. Cyclic AMP-stimulatingGPCRs on β-cells include the GLP-1, GIP, β2-adrenergic receptors andGPR119. Increasing cAMP concentration in β-cells is known to lead to theactivation of PKA which is thought to prevent the opening of potassiumchannels on the surface of the β-cell. The reduction in K⁺ effluxdepolarizes the β-cell leading to an influx of Ca⁺⁺ which promotes therelease of insulin.

GPR119 (e.g., human GPR119, GenBank® Accession No. AAP72125 and allelesthereof; e.g., mouse GPR119, GenBank® Accession No. AY288423 and allelesthereof) is a GPCR located at chromosome position Xp26.1 (Fredricksson,R. et al., “Seven evolutionarily conserved human rhodopsin Gprotein-coupled receptors lacking close relatives”, FEBS Lett.,554:381-388 (2003)). The receptor is coupled to Gs, and when stimulated,produces an elevation in cAMP in a variety of cell types includingβ-cell-derived insulinomas (Soga, T. et al., “Lysophosphatidylcholineenhances glucose-dependent insulin secretion via an orphanG-protein-coupled receptor”, Biochem. Biophys. Res. Comm., 326:744-751(2005), International Patent Applications WO 04/065380, WO 04/076413, WO05/007647, WO 05/007658, WO 05/121121, WO 06/083491, and EP 1338651).The receptor has been shown to be localized to the β-cells of thepancreas in a number of species as well as in specific cell types of thegastrointestinal tract. Activation of GPR119, with agonist ligands suchas lysophosphatidylcholine, produce a glucose dependent increase ininsulin secretion from primary mouse islets and various insulinoma celllines such as NIT-1 and HIT-T15 (Soga, T. et al.,“Lysophosphatidylcholine enhances glucose-dependent insulin secretionvia an orphan G-protein-coupled receptor”, Biochem. Biophys. Res. Comm.,326:744-751 (2005); Chu, Z. L. et al., “A role for β-cell-expressedGPR119 in glycemic control by enhancing glucose-dependent insulinrelease”, Endocrinology, doi:10.1210/en.2006-1608 (2007)).

When activators of GPR119 are administered to either normal mice or micethat are prone to diabetes due to genetic mutation, prior to an oralglucose tolerance test, improvements in glucose tolerance are observed.A short-lived increase in plasma glucagon-like peptide-1 and plasmainsulin levels are also observed in these treated animals (Chu, Z. L. etal., “A role for (3-cell-expressed GPR119 in glycemic control byenhancing glucose-dependent insulin release”, Endocrinology,doi:10.1210/en.2006-1608 (2007)). In addition to effects on plasmaglucose levels, GPR119 activators have also been demonstrated to producereductions in acute food intake and to reduce body weight in ratsfollowing chronic administration (Overton, H. A. et al.,“Deorphanization of a G protein-coupled receptor for oleoylethanolamideand its use in the discovery of small-molecule hypophagic agents”, CellMetabolism, 3:167-175 (2006), WO 05/007647, WO 05/007658).

SUMMARY OF THE INVENTION

In accordance with the present invention, compounds are provided thathave the general structure of Formula I or Formula IA:

wherein n₁, n₂, n₃, G, Q, X, R₁, R₂, R₂₀ and R₂₁ are defined below.

Compounds of the present invention modulate the activity of Gprotein-coupled receptors. Preferably, compounds of the presentinvention modulate the activity of the GPR119 G protein-coupled receptor(“GPR119”). Consequently, the compounds of the present invention may beused in the treatment of multiple diseases or disorders associated withGPR119, such as diabetes and related conditions, microvascularcomplications associated with diabetes, the macrovascular complicationsassociated with diabetes, cardiovascular diseases, Metabolic Syndromeand its component conditions, obesity and other maladies. Examples ofdiseases or disorders associated with the modulation of the GPR119 Gprotein-coupled receptor that can be prevented, modulated, or treatedaccording to the present invention include, but are not limited to,diabetes, hyperglycemia, impaired glucose tolerance, insulin resistance,hyperinsulinemia, retinopathy, neuropathy, nephropathy, delayed woundhealing, atherosclerosis and its sequelae, abnormal heart function,myocardial ischemia, stroke, Metabolic Syndrome, hypertension, obesity,dislipidemia, dyslipidemia, hyperlipidemia, hypertriglyceridemia,hypercholesterolemia, low HDL, high LDL, non-cardiac ischemia,infection, cancer, vascular restenosis, pancreatitis, neurodegenerativedisease, lipid disorders, cognitive impairment and dementia, bonedisease, HIV protease associated lipodystrophy and glaucoma.

In addition, the present invention relates to a formulated productwherein the selected formulation is made by using a compound of FormulaI and/or IA as the only active ingredient or by combining (a) a compoundof Formula I and/or IA (using any of the compound embodiments listedherein) and (b) an additional active ingredient, for example, dipeptidylpeptidase-IV (DPP4) inhibitor (for example a member selected fromsaxagliptin, sitagliptin, vildagliptin and alogliptin).

The present invention provides for compounds of Formula I and IA,pharmaceutical compositions employing such compounds, and for methods ofusing such compounds. In particular, the present invention provides apharmaceutical composition comprising a therapeutically effective amountof a compound of Formula I and/or IA, alone or in combination with apharmaceutically acceptable carrier.

Further, in accordance with the present invention, a method is providedfor preventing, modulating, or treating the progression or onset ofdiseases or disorders associated with the activity of the GPR119 Gprotein-coupled receptor, such as defined above and hereinafter, whereina therapeutically effective amount of a compound of Formula I and/or IAis administered to a mammalian, i.e., human, patient in need oftreatment.

The compounds of the invention can be used alone, in combination withother compounds of the present invention, or in combination with one ormore other agent(s).

Further, the present invention provides a method for preventing,modulating, or treating the diseases as defined above and hereinafter,wherein a therapeutically effective amount of a combination of acompound of Formula I or IA and another compound of Formula I or IAand/or at least one other type of therapeutic agent, is administered toa mammalian, i.e., human, patient in need of treatment.

DESCRIPTION OF THE INVENTION

In accordance with the present invention, compounds of Formula I andFormula IA are provided:

including enantiomers, diastereomers, solvates and salts thereof(particularly enantiomers, diastereomers and pharmaceutically acceptablesalts thereof) having ring A and ring B, wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of VS;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl; and

R₂₀ and R₂₁ are each independently selected from the group consisting ofhydrogen, alkyl, haloalkyl, cycloalkyl, phenyl, halo, —CN, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

The terms “Formula I” and “Formula IA” and all embodiments thereof shallinclude enantiomers, diastereomers, solvates and salts thereof(particularly enantiomers, diastereomers and pharmaceutically acceptablesalts thereof).

In a second embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR_(2i);

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

m is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is a 6-membered monocyclic aryl or a 6-membered monocyclicheteroaryl, each of which may be optionally substituted with one or moremembers selected from R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃, —OR₁₄; —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl; and

R₂₀ and R₂₁ are each independently selected from the group consisting ofhydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a third embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is phenyl, pyridinyl, pyrazinyl or pyrimindinyl, each of which may beoptionally substituted with one or more members selected from R_(1a),R_(1b), R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl; and

R₂₀ and R₂₁ are each independently selected from the group consisting ofhydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a fourth embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is phenyl or pyridinyl, each of which may be optionally substitutedwith one or more members selected from R_(1a), R_(1b), R_(1c), R_(1d)and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄; —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl; and

R₂₀ and R₂₁ are each independently selected from the group consisting ofhydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a fifth embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is

each of which may be optionally substituted with one or more membersselected from the group consisting of R_(1a), R_(1b), R_(1c), R_(1d) andR_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl, wherein theheteroaryl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl; and

R₂₀ and R₂₁ are each independently selected from the group consisting ofhydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a sixth embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR_(2i);

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃, —OR₁₄; —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl; and

R₂₀ and R₂₁ are each independently selected from the group consisting ofhydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a seventh embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is

R_(1a), R_(1b), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl and cycloalkyl may each be optionally substituted withone or more R₆'s; and (b) the alkyl may optionally be substituted by oneor more of R₇'s;

R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) the alkenyl, alkynyl,cycloalkyl, aryl and heterocyclyl may each be optionally substitutedwith one or more R₆'s; and (b) the alkyl may optionally be substitutedby one or more of R₇'s;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl; and

R₂₀ and R₂₁ are each independently selected from the group consisting ofhydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In an eighth embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is aryl, heteroaryl, heterocyclyl, —C(═O)NR₃R₅, —C(═O)R₅ or—C(═O)OR₅, wherein the aryl, heteroaryl and heterocyclyl may each beoptionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃, —OR₁₄; —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄;—S(O)₂NR₁₄C(═O)NR₁₄R₁₄; —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄; —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃, —OR₁₄; —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄;—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀;—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl; and

R₂₀ and R₂₁ are each independently selected from the group consisting ofhydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a ninth embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR_(2i);

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of VS;

R₂ is aryl, heteroaryl or —C(═O)OR₅, wherein the aryl and heteroaryl mayeach be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl; and

R₂₀ and R₂₁ are each independently selected from the group consisting ofhydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a tenth embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is heteroaryl or —C(═O)OR₅, wherein the heteroaryl may be optionallysubstituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl; and

R₂₀ and R₂₁ are each independently selected from the group consisting ofhydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In an eleventh embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is heteroaryl which may be optionally substituted with one or moreR₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl; and

R₂₀ and R₂₁ are each independently selected from the group consisting ofhydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a twelfth embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR_(2i);

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is oxadiazolyl, benzoxazolyl, pyridinyl or pyrimidinyl, each of whichmay be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃, —OR₁₄; —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄;—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉;—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl; and

R₂₀ and R₂₁ are each independently selected from the group consisting ofhydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a thirteenth embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is pyrimidinyl which may be optionally substituted with one or moreR₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a)S;

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl; and

R₂₀ and R₂₁ are each independently selected from the group consisting ofhydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a fourteenth embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR_(2i);

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

m is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of VS;

R₂ is —C(═O)OR₅;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃, —OR₁₄; —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄;—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉;—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl; and

R₂₀ and R₂₁ are each independently selected from the group consisting ofhydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a fifteenth embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is —C(═O)OR₅;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein thealkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃, —OR₁₄; —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄;—S(O)₂NR₁₄C(═O)NR₁₄R₁₄; —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄; —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃, —OR₁₄; —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄;—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀;—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl; and

R₂₀ and R₂₁ are each independently selected from the group consisting ofhydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a sixteenth embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR_(2i);

G is CH or N;

Q is C or N;

X is CH or N, provided that Q and X are not both N;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of VS;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄; —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄;—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉;—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉; —C(═O)R₁₀ and —OC(═O)R₁₀.

In a seventeenth embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C or N;

X is CH;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃, —OR₁₄; —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄;—S(O)₂NR₁₄C(═O)NR₁₄R₁₄; —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄; —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃, —OR₁₄; —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄;—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀;—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In an eighteenth embodiment, compounds of Formula I and Formula IA areprovided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR_(2i);

G is CH or N;

Q is C;

X is CH;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 1-2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of VS;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a nineteenth embodiment, compounds of Formula IA are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C;

X is CH;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃, —OR₁₄; —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄;—S(O)₂NR₁₄C(═O)NR₁₄R₁₄; —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄; —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃, —OR₁₄; —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄;—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀;—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a twentieth embodiment, compounds of Formula I are provided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR_(2i);

G is CH or N;

Q is C;

X is CH;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 0-2;

n₂ is 0-2;

n₃ is 2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of VS;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a twenty-first embodiment, compounds of Formula IA are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C;

X is CH;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 1;

n₂ is 1;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃, —OR₁₄; —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄;—S(O)₂NR₁₄C(═O)NR₁₄R₁₄; —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄; —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃, —OR₁₄; —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄;—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀;—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a twenty-second embodiment, compounds of Formula I are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR_(2i);

G is CH or N;

Q is C;

X is CH;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 1;

n₂ is 1;

n₃ is 2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of VS;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a twenty-third embodiment, compounds of Formula IA are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C;

X is CH;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 1;

n₂ is 1;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a twenty-fourth embodiment, compounds of Formula I are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C;

X is CH;

Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂;

n₁ is 1;

n₂ is 1;

n₃ is 2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a twenty-fifth embodiment, compounds of Formula IA are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C;

X is CH;

Y is O, OCR₉R₉, or S;

n₁ is 1;

n₂ is 1;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a twenty-sixth embodiment, compounds of Formula I are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C;

X is CH;

Y is O, OCR₉R₉ or S;

n₁ is 1;

n₂ is 1;

n₃ is 2;

R₁ is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroarylor a 6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl andheterocyclyl may each be optionally substituted with one or more R₆'s;

R₃ is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a twenty-seventh embodiment, compounds of Formula IA are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C;

X is CH;

Y is O, OCR₉R₉ or S;

n₁ is 1;

n₂ is 1;

R₁ is phenyl or a 6-membered monocyclic heteroaryl, each of which may beoptionally substituted with one or more members selected from R_(1a),R_(1b), R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is heteroaryl or —C(═O)OR₅, wherein the heteroaryl may be optionallysubstituted with one or more R₆'s;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₀, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a twenty-eighth embodiment, compounds of Formula I are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR_(2i);

G is CH or N;

Q is C;

X is CH;

Y is O, OCR₉R₉ or S;

n₁ is 1;

n₂ is 1;

n₃ is 2;

R₁ is phenyl or a 6-membered monocyclic heteroaryl, each of which may beoptionally substituted with one or more members selected from R_(1a),R_(1b), R_(1c), R_(1d) and

R_(1e);

R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s;

R₂ is heteroaryl or —C(═O)OR₅, wherein the heteroaryl may be optionallysubstituted with one or more R₆'s;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₀, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a twenty-ninth embodiment, compounds of Formula IA are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR_(2i);

G is CH or N;

Q is C;

X is CH;

Y is O, OCR₉R₉, or S;

n₁ is 1;

n₂ is 1;

R₁ is phenyl or a 6-membered monocyclic heteroaryl, each of which may beoptionally substituted with one or more members selected from R_(1a),R_(1b), R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl and cycloalkyl may each be optionallysubstituted with one or more R₆'s; and (b) the alkyl may optionally besubstituted by one or more of R₇'s;

R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s;

R₂ is heteroaryl or —C(═O)OR₅, wherein the heteroaryl may be optionallysubstituted with one or more R₆'s;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein thealkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl,cycloalkyl, cycloalkylalkyl and heterocyclyl may each be optionallysubstituted with 0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a thirtieth embodiment, compounds of Formula I are provided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C;

X is CH;

Y is O, OCR₉R₉, or S;

n₁ is 1;

n₂ is 1;

n₃ is 2;

R₁ is phenyl or a 6-membered monocyclic heteroaryl, each of which may beoptionally substituted with one or more members selected from R_(1a),R_(1b), R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl and cycloalkyl may each be optionallysubstituted with one or more R₆'s; and (b) the alkyl may optionally besubstituted by one or more of R₇'s;

R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s;

R₂ is heteroaryl or —C(═O)OR₅, wherein the heteroaryl may be optionallysubstituted with one or more R₆'s;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein thealkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl,cycloalkyl, cycloalkylalkyl and heterocyclyl may each be optionallysubstituted with 0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, eachof which may be optionally substituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a thirty-first embodiment, compounds of Formula IA are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is CH or N;

Q is C;

X is CH;

Y is O, OCR₉R₉ or S;

n₁ is 1;

n₂ is 1;

R₁ is phenyl or a 6-membered monocyclic heteroaryl, each of which may beoptionally substituted with one or more members selected from R_(1a),R_(1b), R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl and cycloalkyl may each be optionallysubstituted with one or more R₆'s; and (b) the alkyl may optionally besubstituted by one or more of R₇'s;

R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s;

R₂ is heteroaryl or —C(═O)OR₅, wherein the heteroaryl may be optionallysubstituted with one or more R₆'s;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein thealkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl,cycloalkyl, cycloalkylalkyl and heterocyclyl may each be optionallysubstituted with 0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl and cycloalkyl, each of which may be optionallysubstituted with one or more R_(8a) s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl, and aryl, wherein the alkyl, cycloalkyl, and aryl may eachbe optionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O;

R₁₀, at each occurrence, is independently selected from alkyl,cycloalkyl, and aryl, which may each be optionally substituted with 0-3R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-3 R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a thirty-second embodiment, compounds of Formula I are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR_(2i);

G is CH or N;

Q is C;

X is CH;

Y is O, OCR₉R₉ or S;

n₁ is 1;

n₂ is 1;

n₃ is 2;

R₁ is phenyl or a 6-membered monocyclic heteroaryl, each of which may beoptionally substituted with one or more members selected from R_(1a),R_(1b), R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl and cycloalkyl may each be optionallysubstituted with one or more R₆'s; and (b) the alkyl may optionally besubstituted by one or more of R₇'s;

R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s;

R₂ is heteroaryl or —C(═O)OR₅, wherein the heteroaryl may be optionallysubstituted with one or more R₆'s;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein thealkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl,cycloalkyl, cycloalkylalkyl and heterocyclyl may each be optionallysubstituted with 0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl and cycloalkyl, each of which may be optionallysubstituted with one or more R_(8a) s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O;

R₁₀, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-3 R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a thirty-third embodiment, compounds of Formula IA are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is N;

Q is C;

X is CH;

Y is O, OCR₉R₉ or S;

n₁ is 1;

n₂ is 1

R₁ is phenyl or a 6-membered monocyclic heteroaryl, each of which may beoptionally substituted with one or more members selected from R_(1a),R_(1b), R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl and cycloalkyl may each be optionallysubstituted with one or more R₆'s; and (b) the alkyl may optionally besubstituted by one or more of R₇'s;

R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s;

R₂ is heteroaryl or —C(═O)OR₅, wherein the heteroaryl may be optionallysubstituted with one or more R₆'s;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein thealkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl,cycloalkyl, cycloalkylalkyl and heterocyclyl may each be optionallysubstituted with 0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl and cycloalkyl, each of which may be optionallysubstituted with one or more R_(8a) s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O;

R₁₀, at each occurrence, is independently selected from alkyl,cycloalkyl, and aryl, which may each be optionally substituted with 0-3R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-3 R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a thirty-fourth embodiment, compounds of Formula I are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR_(2i);

G is N;

Q is C;

X is CH;

Y is O, OCR₉R₉ or S;

n₁ is 1;

n₂ is 1;

n₃ is 2;

R₁ is phenyl or a 6-membered monocyclic heteroaryl, each of which may beoptionally substituted with one or more members selected from R_(1a),R_(1b), R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl and cycloalkyl may each be optionallysubstituted with one or more R₆'s; and (b) the alkyl may optionally besubstituted by one or more of R₇'s;

R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s;

R₂ is heteroaryl or —C(═O)OR₅, wherein the heteroaryl may be optionallysubstituted with one or more R₆'s;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein thealkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl,cycloalkyl, cycloalkylalkyl and heterocyclyl may each be optionallysubstituted with 0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl and cycloalkyl, each of which may be optionallysubstituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O;

R₁₀, at each occurrence, is independently selected from alkyl,cycloalkyl, and aryl, which may each be optionally substituted with 0-3R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-3 R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a thirty-fifth embodiment, compounds of Formula IA are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is N;

Q is C;

X is CH;

Y is O;

n₁ is 1;

n₂ is 1;

R₁ is phenyl or a 6-membered monocyclic heteroaryl, each of which may beoptionally substituted with one or more members selected from R_(1a),R_(1b), R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl and cycloalkyl, may each be optionallysubstituted with one or more R₆'s; and (b) the alkyl may optionally besubstituted by one or more of R₇'s;

R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s;

R₂ is heteroaryl or —C(═O)OR₅, wherein the heteroaryl may be optionallysubstituted with one or more R₆'s;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein thealkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl,cycloalkyl, cycloalkylalkyl and heterocyclyl may each be optionallysubstituted with 0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl and cycloalkyl, each of which may be optionallysubstituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O;

R₁₀, at each occurrence, is independently selected from alkyl,cycloalkyl, and aryl, which may each be optionally substituted with 0-3R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-3 R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a thirty-sixth embodiment, compounds of Formula I are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is N;

Q is C;

X is CH;

Y is O;

n₁ is 1;

n₂ is 1;

n₃ is 2;

R₁ is phenyl or a 6-membered monocyclic heteroaryl, each of which may beoptionally substituted with one or more members selected from R_(1a),R_(1b), R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl and cycloalkyl, may each be optionallysubstituted with one or more R₆'s; and (b) the alkyl may optionally besubstituted by one or more of R₇'s;

R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s;

R₂ is heteroaryl or —C(═O)OR₅, wherein the heteroaryl may be optionallysubstituted with one or more R₆'s;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein thealkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl,cycloalkyl, cycloalkylalkyl and heterocyclyl may each be optionallysubstituted with 0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl and cycloalkyl, each of which may be optionallysubstituted with one or more R_(8a) s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-5R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O;

R₁₀, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-3 R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.

In a thirty-seventh embodiment, compounds of Formula IA are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is N;

Q is C;

X is CH;

Y is O;

n₁ is 1;

n₂ is 1;

R₁ is phenyl or a 6-membered monocyclic heteroaryl, each of which may beoptionally substituted with one or more members selected from R_(1a),R_(1b), R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl and cycloalkyl may each be optionallysubstituted with one or more R₆'s; and (b) the alkyl may optionally besubstituted by one or more of R₇'s;

R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s;

R₂ is heteroaryl or —C(═O)OR₅, wherein the heteroaryl may be optionallysubstituted with one or more R₆'s;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein thealkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl,cycloalkyl, cycloalkylalkyl and heterocyclyl may each be optionallysubstituted with 0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl and cycloalkyl, each of which may be optionallysubstituted with one or more R_(8a) s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O;

R₁₀, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl cycloalkyl and aryl may each beoptionally substituted with 0-3 R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,halo and —CN.

In a thirty-eighth embodiment, compounds of Formula I are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is N;

Q is C;

X is CH;

Y is O;

n₁ is 1;

n₂ is 1;

n₃ is 2;

R₁ is phenyl or a 6-membered monocyclic heteroaryl, each of which may beoptionally substituted with one or more members selected from R_(1a),R_(1b), R_(1c), R_(1d) and R_(1e);

R_(1a), R_(1b), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl and cycloalkyl may each be optionallysubstituted with one or more R₆'s; and (b) the alkyl may optionally besubstituted by one or more of R₇'s;

R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s;

R₂ is heteroaryl or —C(═O)OR₅, wherein the heteroaryl may be optionallysubstituted with one or more R₆'s;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein thealkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl,cycloalkyl, cycloalkylalkyl and heterocyclyl may each be optionallysubstituted with 0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl and cycloalkyl, each of which may be optionallysubstituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O;

R₁₀, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-3 R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,halo and —CN.

In a thirty-ninth embodiment, compounds of Formula IA are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is N;

Q is C;

X is CH;

Y is O;

n₁ is 1;

n₂ is 1;

R₁ is

R_(1a), R_(1b), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl and cycloalkyl may each be optionallysubstituted with one or more R₆'s; and (b) the alkyl may optionally besubstituted by one or more of R₇'s;

R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s;

R₂ is heteroaryl or —C(═O)OR₅, wherein the heteroaryl may be optionallysubstituted with one or more R₆'s;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein thealkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl,cycloalkyl, cycloalkylalkyl and heterocyclyl may each be optionallysubstituted with 0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl and cycloalkyl, each of which may be optionallysubstituted with one or more R_(8a) s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O;

R₁₀, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-3 R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,halo and —CN.

In a fortieth embodiment, compounds of Formula I are provided wherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is N;

Q is C;

X is CH;

Y is O;

n₁ is 1;

n₂ is 1;

n₃ is 2;

R₁ is

R_(1a), R_(1b), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl and cycloalkyl may each be optionallysubstituted with one or more R₆'s; and (b) the alkyl may optionally besubstituted by one or more of R₇'s;

R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s;

R₂ is heteroaryl or —C(═O)OR₅, wherein the heteroaryl may be optionallysubstituted with one or more R₆'s;

R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, eachof which may be optionally substituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein thealkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl,cycloalkyl, cycloalkylalkyl and heterocyclyl may each be optionallysubstituted with 0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl and cycloalkyl, each of which may be optionallysubstituted with one or more R_(8a)'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈, ═O;

R₁₀, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, and —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-3 R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,halo and —CN.

In a forty-first embodiment, compounds of Formula IA are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR₂₁;

G is N;

Q is C;

X is CH;

Y is O;

n₁ is 1;

n₂ is 1:

R₁ is

R_(1a), R_(1b), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl and cycloalkyl may each be optionallysubstituted with one or more R₆'s; and (b) the alkyl may optionally besubstituted by one or more of R₇'s;

R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s;

R₂ is pyridinyl, pyrimidinyl or —C(═O)OR₅, wherein the pyridinyl andpyrimidinyl may each be optionally substituted with one or more R₆'s;

R₅ is alkyl, aryl or cycloalkyl, each of which may be optionallysubstituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein thealkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl,cycloalkyl, cycloalkylalkyl and heterocyclyl may each be optionallysubstituted with 0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl and cycloalkyl, each of which may be optionallysubstituted with one or more R₈'s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O;

R₁₀, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-3 R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,halo and —CN.

In a forty-second embodiment, compounds of Formula I are providedwherein:

ring A is optionally substituted with one or more R's shown as R₂₀ andR_(2i);

G is N;

Q is C;

X is CH;

Y is O;

n₁ is 1;

n₂ is 1;

n₃ is 2;

R₁ is

R_(1a), R_(1b), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl and cycloalkyl may each be optionallysubstituted with one or more R₆'s; and (b) the alkyl may optionally besubstituted by one or more of R₇'s;

R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s;

R₂ is pyridinyl, pyrimidinyl or —C(═O)OR₅, wherein the pyridinyl andpyrimidinyl may each be optionally substituted with one or more R₆'s;

R₅ is alkyl, aryl or cycloalkyl, each of which may be optionallysubstituted with one or more R₆'s;

R₆, at each occurrence, is independently selected from alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN, —C(═O)OR₁₀,—OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein thealkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-5 R_(9a);

R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl,cycloalkyl, cycloalkylalkyl and heterocyclyl may each be optionallysubstituted with 0-5 R_(9a);

R₈, at each occurrence, is independently selected from the groupconsisting of alkyl and cycloalkyl, each of which may be optionallysubstituted with one or more R_(8a) s;

R_(8a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄;

R₉, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-5 R_(9a);

R_(9a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O;

R₁₀, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(10a);

R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₁, at each occurrence, is independently selected from alkyl,cycloalkyl and aryl, which may each be optionally substituted with 0-3R_(11a);

R_(11a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈;

R₁₂, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl, wherein the alkyl, cycloalkyl and aryl may each beoptionally substituted with 0-3 R_(10a);

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl,cycloalkyl and aryl;

R₂₀ is hydrogen; and

R₂₁ is selected from the group consisting of hydrogen, alkyl, haloalkyl,halo and —CN.

One particular group of compounds is the group of embodiments of FormulaI.

Another particular group of compounds is the group of embodiments ofFormula IA (noting that for Formula IA there is no n₃ in the formula).

For each of the embodiments described in this application, further andmore particular values of the terms used in each of the embodiments maybe selected from the following definitions; these values may be usedindividually in any of the embodiments or in any combination. It isnoted that for any occurrences of “═O”, these may be used with suitableaccommodation in the bond structure at that site as will be appreciatedby those skilled in the art.

The heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl usedin each occurrence may each contain 1-4 heteroatoms selected from N, Oand S.

R₁ may be selected from phenyl and a 6 membered monocyclic heteroarylhaving 1 or 2 N's wherein:

a) phenyl and heteroaryl may each be substituted with 1-3 of R_(1a),R_(1b), R_(1c), R_(1d) and R_(1e); and

b) R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from hydrogen, C₁₋₃ alkyl, C₃₋₆ cycloalkyl, phenyl, halo, —CN,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈,NR₉C(═O)NR₉R₉ and —NR₉S(O₂)R₈ wherein:

-   -   i) R₈ is selected from the group consisting of C₁₋₆ straight and        branched chain alkyl and C₃₋₆ cycloalkyl each of which may be        optionally substituted with one or more R_(8a), where R_(8a) is        selected from halo, C₁₋₃ haloalkyl, C₃₋₆ cycloalkyl, OH, C₁₋₃        alkoxy and CN;    -   ii) R₉ is selected from the group consisting of C₁₋₆ straight        and branched chain alkyl and C₃₋₆ cycloalkyl each of which may        be optionally substituted with one or more R_(9a), where R_(9a)        is selected from halo, C₁₋₃ haloalkyl, C₃₋₆ cycloalkyl, OH, C₁₋₃        alkoxy and CN;    -   iii) R₁₀ is selected from the group consisting of C₁₋₆ straight        and branched chain alkyl and C₃₋₆ cycloalkyl each of which may        be optionally substituted with one or more R_(10a) where R_(10a)        is selected from halo, C₁₋₃ haloalkyl, C₃₋₆ cycloalkyl, OH, C₁₋₃        alkoxy and CN;    -   iv) R₁₁ is selected from the group consisting of C₁₋₆ straight        and branched chain alkyl and C₃₋₆ cycloalkyl each of which may        be optionally substituted with one or more R_(11a), where        R_(11a) is selected from halo, C₁₋₃ haloalkyl, C₃₋₆ cycloalkyl,        OH, C₁₋₃ alkoxy and CN; and    -   v) R₁₂ is selected from the group consisting of C₁₋₆ straight        and branched chain alkyl and C₃₋₆ cycloalkyl each of which may        be optionally substituted with one or more R_(10a), where        R_(10a) is selected from halo, C₁₋₃ haloalkyl, C₃₋₆ cycloalkyl,        OH, C₁₋₃ alkoxy and CN.

R₂ may be selected from —C(═O)OR₅, a 5-6 membered monocyclic heteroarylhaving 1-3 heteroatoms selected from O and N; and an 8-10 bicyclicheteroaryl having 1-3 heteroatoms selected from O and N, wherein:

i) the heteroaryls may be each be substituted with 1 or 2 of R₆, whereR₆ is selected from C₁₋₆ alkyl, C₁₋₃ haloalkyl, phenyl, C₃₋₆ cycloalkyl,halo, —CN, —OCF₃ and —OC₁₋₅alkyl, wherein the alkyl, phenyl, andcycloalkyl values for R₆ may each be optionally substituted with 0-2R_(9a) where R_(9a) is selected from halo, C₁₋₃ haloalkyl, C₃₋₆cycloalkyl, OH, C₁₋₃ alkoxy and CN; and

ii) R₅ is selected from the group consisting of C₁₋₆ straight andbranched chain alkyl, C₃₋₆ cycloalkyl and phenyl wherein the alkyl,phenyl, and cycloalkyl, may each be optionally substituted with 0-2 R₆wherein R₆ is as defined in i).

R₅ may be selected from the group consisting of C₁₋₆ straight andbranched chain alkyl, C₃₋₆ cycloalkyl and phenyl wherein:

i) the alkyl, phenyl, and cycloalkyl, may each be optionally substitutedwith 0-2 R₆;

ii) R₆ is selected from C₁₋₆ straight and branched chain alkyl; C₃₋₆cycloalkyl; C₂₋₆ alkenyl; C₂₋₆ alkynyl; OH; phenyl; halo; C₁₋₆haloalkyl; 5-6 membered heteroaryl having carbon atoms and 1-2heteroatoms selected from O, S and N; 5-6 membered heterocycle havingcarbon atoms and 1-2 heteroatoms selected from O and N; OCF₃; OR₁₀ whereR₁₀ is C₁₋₃ alkyl or C₃₋₆ cycloalkyl; and SR₁₀ where R₁₀ is C₁₋₃ alkylor C₃₋₆ cycloalkyl; and

iii) the alkyl, alkenyl, alkynyl, phenyl, cycloalkyl, heteroaryl andheterocyclyl values of R₆ may each be optionally substituted with 0-3R_(9a), where R_(9a) is selected from the group consisting of halo, C₁₋₃haloalkyl, C₃₋₆ cycloalkyl, OH, C₁₋₃ alkoxy CN and ═O.

R₆ may be selected from C₁₋₆ straight and branched chain alkyl; C₃₋₆cycloalkyl; C₂₋₆ alkenyl; C₂₋₆ alkynyl; OH; phenyl; halo; C₁₋₆haloalkyl; 5-6 membered heteroaryl having carbon atoms and 1-2heteroatoms selected from O, S and N; 5-6 membered heterocycle havingcarbon atoms and 1-2 heteroatoms selected from O and N; OCF₃; OR₁₀ whereR₁₀ is C₁₋₃ alkyl or C₃₋₆ cycloalkyl; and SR₁₀ where R₁₀ is C₁₋₃ alkylor C₃₋₆ cycloalkyl; and further wherein the alkyl, alkenyl, alkynyl,phenyl, cycloalkyl, heteroaryl and heterocyclyl values of R₆ may each beoptionally substituted with 0-3 R_(9a), where R_(9a) is selected fromthe group consisting of halo, C₁₋₃ haloalkyl, C₃₋₆ cycloalkyl, OH, C₁₋₃alkoxy, CN and ═O.

R₇ may be selected from the group consisting of C₁₋₆ straight andbranched chain alkyl; C₃₋₆ cycloalkyl; C₂₋₆ alkenyl; C₂₋₆ alkynyl; OH;phenyl; halo; Cl_(—)6 haloalkyl; 5-6 membered heterocycle having carbonatoms and 1-2 heteroatoms selected from O and N; OCF₃; OR₁₀ where R₁₀ isC₁₋₃ alkyl or C₃₋₆ cycloalkyl; and SR₁₀ where R₁₀ is C₁₋₃ alkyl or C₃₋₆cycloalkyl; and further, where the alkyl, alkenyl, alkynyl, phenyl,cycloalkyl and heterocyclyl values of R₇ may each be optionallysubstituted with 0-3 R_(9a), where R_(9a) is selected from the groupconsisting of halo, C₁₋₃ haloalkyl, C₃₋₆ cycloalkyl, OH, C₁₋₃ alkoxy, CNand ═O.

R₈ is selected from the group consisting of C₁₋₆ straight and branchedchain alkyl and C₃₋₆ cycloalkyl each of which may be optionallysubstituted with one or more R_(8a)'s where R_(8a) is selected fromhalo, C₁₋₃ haloalkyl, C₃₋₆ cycloalkyl, OH, C₁₋₃ alkoxy, CN and ═O.

R_(8a) is selected from halo, C₁₋₃ haloalkyl, C₃₋₆ cycloalkyl, OH, C₁₋₃alkoxy, CN and ═O.

R₉ is selected from H, C₁₋₃ straight and branched chain alkyl and C₃₋₆cycloalkyl.

R_(9a) is selected from halo, C₁₋₃ haloalkyl, C₃₋₆ cycloalkyl, OH, C₁₋₃alkoxy, CN and ═O.

R₁₀ is selected from C₁₋₃ straight and branched chain alkyl and C₃₋₆cycloalkyl.

R_(10a) is selected from halo, C₁₋₃ haloalkyl, C₃₋₆ cycloalkyl, OH, C₁₋₃alkoxy, CN and ═O.

R₁₁ is selected from C₁₋₃ straight and branched chain alkyl and C₃₋₆cycloalkyl.

R_(11a) is selected from halo, C₁₋₃ haloalkyl, C₃₋₆ cycloalkyl, OH, C₁₋₃alkoxy, CN and ═O.

R₁₂ is selected from the group consisting of C₁₋₃ straight and branchedchain alkyl and C₃₋₆ cycloalkyl.

R₁₄ is H.

R₂₀ is H.

R₂₁ is selected from H, C₁₋₃ alkyl, C₃₋₆ cycloalkyl, halo and CN.

In a forty-third embodiment, compounds of the present invention areselected from the group of compounds exemplified in the Examples.

In a forty-fourth embodiment, the present invention relates topharmaceutical compositions comprised of a therapeutically effectiveamount of a compound of the present invention, alone or, optionally, incombination with a pharmaceutically acceptable carrier and/or one ormore other agent(s), for example, a glucagon-like peptide-1 receptoragonist or fragment thereof.

In a forty-fifth embodiment, the present invention relates to methods ofmodulating the activity of the GPR119 G protein-coupled receptorcomprising administering to a mammalian patient, for example, a humanpatient, in need thereof a therapeutically effective amount of acompound of the present invention, alone, or optionally, in combinationwith another compound of the present invention and/or at least one othertype of therapeutic agent.

In a forty-sixth embodiment, the present invention relates to a methodfor preventing, modulating, or treating the progression or onset ofdiseases or disorders associated with the activity of the GPR119 Gprotein-coupled receptor comprising administering to a mammalianpatient, for example, a human patient, in need of prevention,modulation, or treatment a therapeutically effective amount of acompound of the present invention, alone, or, optionally, in combinationwith another compound of the present invention and/or at least one othertype of therapeutic agent.

Examples of diseases or disorders associated with the activity of theGPR119 G protein-coupled receptor that can be prevented, modulated, ortreated according to the present invention include, but are not limitedto, diabetes, hyperglycemia, impaired glucose tolerance, insulinresistance, hyperinsulinemia, retinopathy, neuropathy, nephropathy,delayed wound healing, atherosclerosis and its sequelae, abnormal heartfunction, myocardial ischemia, stroke, Metabolic Syndrome, hypertension,obesity, dislipidemia, dyslipidemia, hyperlipidemia,hypertriglyceridemia, hypercholesterolemia, low HDL, high LDL,non-cardiac ischemia, infection, cancer, vascular restenosis,pancreatitis, neurodegenerative disease, lipid disorders, cognitiveimpairment and dementia, bone disease, HIV protease associatedlipodystrophy and glaucoma.

In a forty-seventh embodiment, the present invention relates to a methodfor preventing, modulating, or treating the progression or onset ofdiabetes, hyperglycemia, obesity, dyslipidemia, hypertension andcognitive impairment comprising administering to a mammalian patient,for example, a human patient, in need of prevention, modulation, ortreatment a therapeutically effective amount of a compound of thepresent invention, alone, or, optionally, in combination with anothercompound of the present invention and/or at least one other type oftherapeutic agent.

In a forty-eighth embodiment, the present invention relates to a methodfor preventing, modulating, or treating the progression or onset ofdiabetes, comprising administering to a mammalian patient, for example,a human patient, in need of prevention, modulation, or treatment atherapeutically effective amount of a compound of the present invention,alone, or, optionally, in combination with another compound of thepresent invention and/or at least one other type of therapeutic agent.

In a forty-ninth embodiment, the present invention relates to a methodfor preventing, modulating, or treating the progression or onset ofhyperglycemia comprising administering to a mammalian patient, forexample, a human patient, in need of prevention, modulation, ortreatment a therapeutically effective amount of a compound of thepresent invention, alone, or, optionally, in combination with anothercompound of the present invention and/or at least one other type oftherapeutic agent.

In a fiftieth embodiment, the present invention relates to a method forpreventing, modulating, or treating the progression or onset of obesitycomprising administering to a mammalian patient, for example, a humanpatient, in need of prevention, modulation, or treatment atherapeutically effective amount of a compound of the present invention,alone, or, optionally, in combination with another compound of thepresent invention and/or at least one other type of therapeutic agent.

In a fifty-first embodiment, the present invention relates to a methodfor preventing, modulating, or treating the progression or onset ofdyslipidemia comprising administering to a mammalian patient, forexample, a human patient, in need of prevention, modulation, ortreatment a therapeutically effective amount of a compound of thepresent invention, alone, or, optionally, in combination with anothercompound of the present invention and/or at least one other type oftherapeutic agent.

In a fifty-second embodiment, the present invention relates to a methodfor preventing, modulating, or treating the progression or onset ofhypertension comprising administering to a mammalian patient, forexample, a human patient, in need of prevention, modulation, ortreatment a therapeutically effective amount of a compound of thepresent invention, alone, or, optionally, in combination with anothercompound of the present invention and/or at least one other type oftherapeutic agent.

In a fifty-third embodiment, the present invention relates to aformulated product wherein the selected formulation is made by combining(a) a compound of Formula I or IA (using any of the compound embodimentslisted above) and (b) a dipeptidyl peptidase-IV (DPP4) inhibitor (forexample a member selected from saxagliptin, sitagliptin, vildagliptinand alogliptin).

The invention may be embodied in other specific forms without departingfrom the spirit or essential attributes thereof. This invention alsoencompasses all combinations of alternative aspects of the inventionnoted herein. It is understood that any and all embodiments of thepresent invention may be taken in conjunction with any other embodimentto describe additional embodiments of the present invention.Furthermore, any elements of an embodiment may be combined with any andall other elements from any of the embodiments to describe additionalembodiments.

DEFINITIONS

The compounds herein described may have asymmetric centers. Compounds ofthe present invention containing an asymmetrically substituted atom maybe isolated in optically active or racemic forms. It is well known inthe art how to prepare optically active forms, such as by resolution ofracemic forms or by synthesis from optically active starting materials.Many geometric isomers of olefins, C═N double bonds, and the like canalso be present in the compounds described herein, and all such stableisomers are contemplated in the present invention. Cis and transgeometric isomers of the compounds of the present invention aredescribed and may be isolated as a mixture of isomers or as separatedisomeric forms. All chiral, diastereomeric, racemic forms and allgeometric isomeric forms of a structure are intended, unless thespecific stereochemistry or isomeric form is specifically indicated.

One enantiomer of a compound of Formula I or Formula IA may displaysuperior activity compared with the other. Thus, all of thestereochemistries are considered to be a part of the present invention.When required, separation of the racemic material can be achieved byhigh performance liquid chromatography (HPLC) using a chiral column orby a resolution using a resolving agent such as camphonic chloride as inYoung, S. D. et al., Antimicrobial Agents and Chemotherapy, 2602-2605(1995).

To the extent that compounds of Formula I and IA, and salts thereof, mayexist in their tautomeric form, all such tautomeric forms arecontemplated herein as part of the present invention.

The term “substituted”, as used herein, means that any one or morehydrogens on the designated atom or ring is replaced with a selectionfrom the indicated group, provided that the designated atom's or ringatom's normal valency is not exceeded, and that the substitution resultsin a stable compound. When a substituent is keto (i.e., ═O), then 2hydrogens on the atom are replaced.

When any variable (e.g., R₄) occurs more than one time in anyconstituent or formula for a compound, its definition at each occurrenceis independent of its definition at every other occurrence. Thus, forexample, if a group is shown to be substituted with (R₄)_(m) and m is0-3, then said group may optionally be substituted with up to three R₄groups and R₄ at each occurrence is selected independently from thedefinition of R₄. Also, combinations of substituents and/or variablesare permissible only if such combinations result in stable compounds.

When a bond to a substituent is shown to cross a bond connecting twoatoms in a ring, then such substituent may be bonded to any atom on thering. When a substituent is listed without indicating the atom via whichsuch substituent is bonded to the rest of the compound of a givenformula, then such substituent may be bonded via any atom in suchsubstituent. Combinations of substituents and/or variables arepermissible only if such combinations result in stable compounds.

As used herein, “alkyl” is intended to include both branched andstraight-chain saturated aliphatic hydrocarbon groups containing 1 to 20carbons, preferably 1 to 10 carbons, more preferably 1 to 8 carbons, inthe normal chain, such as methyl, ethyl, propyl, isopropyl, butyl,t-butyl, isobutyl, pentyl, hexyl, isohexyl, heptyl, 4,4-dimethylpentyl,octyl, 2,2,4-trimethyl-pentyl, nonyl, decyl, undecyl, dodecyl, thevarious branched chain isomers thereof, and the like as well as suchgroups may optionally include 1 to 4 substituents such as halo, forexample F, Br, Cl, or I, or CF₃, alkyl, alkoxy, aryl, aryloxy,aryl(aryl) or diaryl, arylalkyl, arylalkyloxy, alkenyl, cycloalkyl,cycloalkylalkyl, cycloalkylalkyloxy, amino, hydroxy, hydroxyalkyl, acyl,heteroaryl, heteroaryloxy, heteroarylalkyl, heteroarylalkoxy,aryloxyalkyl, alkylthio, arylalkylthio, aryloxyaryl, alkylamido,alkanoylamino, arylcarbonylamino, nitro, cyano, thiol, haloalkyl,trihaloalkyl, and/or alkylthio.

Unless otherwise indicated, the term “alkenyl” as used herein by itselfor as part of another group refers to straight or branched chainradicals of 2 to 20 carbons, preferably 2 to 12 carbons, and morepreferably 2 to 8 carbons in the normal chain, which include one to sixdouble bonds in the normal chain, such as vinyl, 2-propenyl, 3-butenyl,2-butenyl, 4-pentenyl, 3-pentenyl, 2-hexenyl, 3-hexenyl, 2-heptenyl,3-heptenyl, 4-heptenyl, 3-octenyl, 3-nonenyl, 4-decenyl, 3-undecenyl,4-dodecenyl, 4,8,12-tetradecatrienyl, and the like, and which may beoptionally substituted with 1 to 4 substituents, namely, halogen,haloalkyl, alkyl, alkoxy, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl,amino, hydroxy, heteroaryl, cycloheteroalkyl, alkanoylamino, alkylamido,arylcarbonyl-amino, nitro, cyano, thiol, alkylthio, and/or any of thealkyl substituents set out herein.

Unless otherwise indicated, the term “alkynyl” as used herein by itselfor as part of another group refers to straight or branched chainradicals of 2 to 20 carbons, preferably 2 to 12 carbons and morepreferably 2 to 8 carbons in the normal chain, which include one triplebond in the normal chain, such as 2-propynyl, 3-butynyl, 2-butynyl,4-pentynyl, 3-pentynyl, 2-hexynyl, 3-hexynyl, 2-heptynyl, 3-heptynyl,4-heptynyl, 3-octynyl, 3-nonynyl, 4-decynyl, 3-undecynyl, 4-dodecynyl,and the like, and which may be optionally substituted with 1 to 4substituents, namely, halogen, haloalkyl, alkyl, alkoxy, alkenyl,alkynyl, aryl, arylalkyl, cycloalkyl, amino, heteroaryl,cycloheteroalkyl, hydroxy, alkanoylamino, alkylamido, arylcarbonylamino,nitro, cyano, thiol, and/or alkylthio, and/or any of the alkylsubstituents set out herein.

Unless otherwise indicated, the term “cycloalkyl” as employed hereinalone or as part of another group includes saturated or partiallyunsaturated (containing 1 or 2 double bonds) cyclic hydrocarbon groupscontaining 1 to 10 rings, preferably 1 to 3 rings, including monocyclicalkyl, bicyclic alkyl (or bicycloalkyl) and tricyclic alkyl, containinga total of 3 to 20 carbons forming the ring, preferably 3 to 15 carbons,more preferably 3 to 10 carbons, forming the ring and which may be fusedto 1 or 2 aromatic rings as described for aryl, which includescyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, cyclodecyl, cyclododecyl, cyclohexenyl,

any of which groups may be optionally substituted with 1 to 4substituents such as halogen, alkyl, alkoxy, hydroxy, aryl, aryloxy,arylalkyl, cycloalkyl, alkylamido, alkanoylamino, oxo, acyl,arylcarbonylamino, amino, nitro, cyano, thiol, and/or alkylthio, and/orany of the substituents for alkyl.

Where alkyl groups as defined above have single bonds for attachment toother groups at two different carbon atoms, they are termed “alkylene”groups and may optionally be substituted as defined above for “alkyl”.

Where alkenyl groups as defined above and alkynyl groups as definedabove, respectively, have single bonds for attachment at two differentcarbon atoms, they are termed “alkenylene groups” and “alkynylenegroups”, respectively, and may optionally be substituted as definedabove for “alkenyl” and “alkynyl”.

“Halo” or “halogen” as used herein refers to fluoro, chloro, bromo andiodo; and “haloalkyl” is intended to include both branched andstraight-chain saturated aliphatic hydrocarbon groups, for example CF₃,having the specified number of carbon atoms, substituted with 1 or morehalogen (for example —C_(v)F_(w) where v=1 to 3 and w=1 to (2v+1)).

Unless otherwise indicated, the term “aryl” as employed herein alone oras part of another group refers to monocyclic and bicyclic aromaticgroups containing 6 to 10 carbons in the ring portion (such as phenyl ornaphthyl, including 1-naphthyl and 2-naphthyl) and may optionallyinclude 1 to 3 additional rings fused to a carbocyclic ring or aheterocyclic ring (such as aryl, cycloalkyl, heteroaryl orcycloheteroalkyl rings for example

and may be optionally substituted through available carbon atoms with 1,2 or 3 substituents, for example, hydrogen, halo, haloalkyl, alkyl,haloalkyl, alkoxy, haloalkoxy, alkenyl, trifluoromethyl,trifluoromethoxy, alkynyl, cycloalkyl-alkyl, cycloheteroalkyl,cycloheteroalkylalkyl, aryl, heteroaryl, arylalkyl, aryloxy,aryloxyalkyl, arylalkoxy, arylthio, arylazo, heteroarylalkyl,heteroarylalkenyl, heteroarylheteroaryl, heteroaryloxy, hydroxy, nitro,cyano, amino, substituted amino wherein the amino includes 1 or 2substituents (which are alkyl, aryl, or any of the other aryl compoundsmentioned in the definitions), thiol, alkylthio, arylthio,heteroarylthio, arylthioalkyl, alkoxyarylthio, alkylcarbonyl,arylcarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkoxycarbonyl,aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, alkylcarbonylamino,arylcarbonylamino, arylsulfinyl, arylsulfinylalkyl, arylsulfonylamino orarylsulfonaminocarbonyl and/or any of the alkyl substituents set outherein.

Unless otherwise indicated, the term “lower alkoxy”, “alkoxy”, “aryloxy”or “aralkoxy” as employed herein alone or as part of another groupincludes any of the above alkyl, aralkyl or aryl groups linked to anoxygen atom.

Unless otherwise indicated, the term “amino” as employed herein alone oras part of another group refers to amino that may be substituted withone or two substituents, which may be the same or different, such asalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloheteroalkyl,cycloheteroalkylalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl,hydroxyalkyl, alkoxyalkyl or thioalkyl. In addition, the aminosubstituents may be taken together with the nitrogen atom to which theyare attached to form 1-pyrrolidinyl, 1-piperidinyl, 1-azepinyl,4-morpholinyl, 4-thiamorpholinyl, 1-piperazinyl, 4-alkyl-1-piperazinyl,4-arylalkyl-1-piperazinyl, 4-diarylalkyl-1-piperazinyl, 1-pyrrolidinyl,1-piperidinyl, or 1-azepinyl, optionally substituted with alkyl, alkoxy,alkylthio, halo, trifluoromethyl or hydroxy.

Unless otherwise indicated, the term “lower alkylthio”, “alkylthio”,“arylthio” or “aralkylthio” as employed herein alone or as part ofanother group includes any of the above alkyl, aralkyl or aryl groupslinked to a sulfur atom.

Unless otherwise indicated, the term “lower alkylamino”, “alkylamino”,“arylamino” or “arylalkylamino” as employed herein alone or as part ofanother group includes any of the above alkyl, aryl, or arylalkyl groupslinked to a nitrogen atom.

As used herein, the term “heterocyclyl” or “heterocyclic system” isintended to mean a stable 4- to 14-membered monocyclic, bicyclic ortricyclic heterocyclic ring which is saturated or partially unsaturatedand which consists of carbon atoms and 1, 2, 3, or 4 heteroatomsindependently selected from the group consisting of N, NH, O and S andincluding any bicyclic group in which any of the above-definedheterocyclic rings is fused to a benzene ring. The nitrogen and sulfurheteroatoms may optionally be oxidized. The heterocyclic ring may beattached to its pendant group at any heteroatom or carbon atom, whichresults in a stable structure. The heterocyclic rings described hereinmay be substituted on carbon or on a nitrogen atom if the resultingcompound is stable. If specifically noted, a nitrogen in the heterocyclemay optionally be quaternized. It is preferred that when the totalnumber of S and O atoms in the heterocycle exceeds 1, then theseheteroatoms are not adjacent to one another.

Examples of heterocycles include, but are not limited to, pyrrolidonyl,4-piperidonyl, chromanyl, decahydroquinolinyl,dihydrofuro[2,3-b]tetrahydrofuran, indolinyl, isochromanyl,isoindolinyloctahydroisoquinolinyl, piperazinyl, piperidinyl,piperidonyl, 4-piperidonyl, tetrahydrofuranyl, tetrahydroisoquinolinyl,tetrahydroquinolinyl, morpholinyl, dihydrofuranyl, tetrahydrothiophenyl,pyranyl, dihydropyranyl, 1,4-dioxanyl and 1,3-dioxanyl. Also includedare fused ring and spiro compounds containing, for example, the aboveheterocycles.

As used herein, the term “aromatic heterocyclic system” or “heteroaryl”is intended to mean a stable 5- to 7-membered monocyclic or bicyclic or7- to 10-membered bicyclic heterocyclic aromatic ring which consists ofcarbon atoms and from 1 to 4 heteroatoms independently selected from thegroup consisting of N, O and S and is aromatic in nature.

Examples of heteroaryls are 1H-indazole, 2H,6H-1,5,2-dithiazinyl,indolyl, 4aH-carbazole, 4H-quinolizinyl, 6H-1,2,5-thiadiazinyl,acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl,benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl,benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl,carbazolyl, 4aH-carbazolyl, β-carbolinyl, chromanyl, chromenyl,cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl,imidazolinyl, imidazolyl, indazolyl, indolenyl, indolinyl, indolizinyl,indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl,isoindolyl, isoquinolinyl (benzimidazolyl), isothiazolyl, isoxazolyl,morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinylperimidinyl,phenanthridinyl, phenanthrolinyl, phenarsazinyl, phenazinyl,phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl,piperidinyl, pteridinyl, pteridinyl, purinyl, pyranyl, pyrazinyl,pyrazolidinyl, pyrazolinyl, pyrazolyl, pyrazolotriazinyl, pyridazinyl,pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl,pyrimidinyl, pyrrolidinyl, quinazolinyl, quinolinyl, 4H-quinolizinyl,quinoxalinyl, quinuclidinyl, carbolinyl, 6H-1,2,5-thiadiazinyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl,thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl,1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl,tetrazolyl, and xanthenyl. In another aspect of the invention, examplesof heteroaryls are indolyl, benzimidazolyl, benzofuranyl,benzothiofuranyl, benzoxazolyl, benzthiazolyl, benztriazolyl,benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl,cinnolinyl, furanyl, imidazolyl, indazolyl, indolyl, isoquinolinylisothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl,pyrazolotriazinyl, pyridazinyl, pyridyl, pyridinyl, pyrimidinyl,pyrrolyl, quinazolinyl, quinolinyl, thiazolyl, thienyl and tetrazolyl.

The term “heterocyclylalkyl” as used herein alone or as part of anothergroup refers to heterocyclyl groups as defined above linked through a Catom or heteroatom to an alkyl chain.

The term “heteroarylalkyl” or “heteroarylalkenyl” as used herein aloneor as part of another group refers to a heteroaryl group as definedabove linked through a C atom or heteroatom to an alkyl chain, alkyleneor alkenylene as defined above.

The term “cyano” as used herein refers to a —CN group.

The term “nitro” as used herein refers to an —NO₂ group.

The term “hydroxy” as used herein refers to an —OH group.

The phrase “pharmaceutically acceptable” is employed herein to refer tothose compounds, materials, compositions and/or dosage forms which are,within the scope of sound medical judgment, suitable for use in contactwith the tissues of human beings and animals without excessive toxicity,irritation, allergic response, or other problem or complication,commensurate with a reasonable benefit/risk ratio.

As used herein, “pharmaceutically acceptable salts” refer to derivativesof the disclosed compounds wherein the parent compound is modified bymaking acid or base salts thereof. Examples of pharmaceuticallyacceptable salts include, but are not limited to, mineral or organicacid salts of basic residues such as amines; alkali or organic salts ofacidic residues such as carboxylic acids; and the like. Thepharmaceutically acceptable salts include the conventional non-toxicsalts or the quaternary ammonium salts of the parent compound formed,for example, from non-toxic inorganic or organic acids. For example,such conventional non-toxic salts include those derived from inorganicacids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric,nitric and the like; and the salts prepared from organic acids such asacetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric,citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic,benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric,toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionicand the like.

The pharmaceutically acceptable salts of the present invention can besynthesized from the parent compound which contains a basic or acidicmoiety by conventional chemical methods. Generally, such salts can beprepared by reacting the free acid or base forms of these compounds witha stoichiometric amount of the appropriate base or acid in water or inan organic solvent, or in a mixture of the two; generally, nonaqueousmedia like ether, ethyl acetate, ethanol, isopropanol, or acetonitrileare preferred. Lists of suitable salts are found in Remington'sPharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa.,p. 1418 (1985), the disclosure of which is hereby incorporated byreference.

Any compound that can be converted in vivo to provide the bioactiveagent (i.e., a compound of Formula I or IA) is a prodrug within thescope and spirit of the invention.

The term “prodrug(s)” as employed herein includes esters and carbonatesformed by reacting one or more hydroxyls of compounds of Formula I or IAwith alkyl, alkoxy or aryl substituted acylating agents employingprocedures known to those skilled in the art to generate acetates,pivalates, methylcarbonates, benzoates, and the like.

Various forms of prodrugs are well known in the art and are describedin:

-   a) The Practice of Medicinal Chemistry, Camille G. Wermuth et al.,    Ch. 31 (Academic Press, 1996);-   b) Design of Prodrugs, edited by H. Bundgaard, (Elsevier, 1985);-   c) A Textbook of Drug Design and Development, P. Krogsgaard-Larson    and H. Bundgaard, eds. Ch. 5, pp. 113-191 (Harwood Academic    Publishers, 1991); and-   d) Hydrolysis in Drug and Prodrug Metabolism, Bernard Testa and    Joachim M. Mayer, (Wiley-VCH, 2003).    Said references are incorporated herein by reference, particularly    as to the description of prodrugs.

In addition, compounds of Formula I and IA are, subsequent to theirpreparation, preferably isolated and purified to obtain a compositioncontaining an amount by weight equal to or greater than 99% of acompound of Formula I or IA (“substantially pure” compound), which isthen used or formulated as described herein. Such “substantially pure”compounds of Formula I and IA are also contemplated herein as part ofthe present invention.

All stereoisomers of the compounds of the instant invention arecontemplated, either in admixture or in pure or substantially pure form.The compounds of the present invention can have asymmetric centers atany of the carbon atoms including any one of the R substituents and/orexhibit polymorphism. Consequently, compounds of Formula I and IA canexist in enantiomeric, or diastereomeric forms, or in mixtures thereof.The processes for preparation can utilize racemates, enantiomers, ordiastereomers as starting materials. When diastereomeric or enantiomericproducts are prepared, they can be separated by conventional methods forexample, chromatographic or fractional crystallization.

“Stable compound” and “stable structure” are meant to indicate acompound that is sufficiently robust to survive isolation to a usefuldegree of purity from a reaction mixture, and formulation into anefficacious therapeutic agent. The present invention is intended toembody stable compounds.

“Therapeutically effective amount” is intended to include an amount of acompound of the present invention alone or an amount of the combinationof compounds claimed or an amount of a compound of the present inventionin combination with other active ingredients effective to modulateGPR119 or effective to treat or prevent various disorders.

As used herein, “treating” or “treatment” covers the treatment of adisease-state in a mammal, particularly in a human, and include: (a)preventing the disease-state from occurring in a mammal, in particular,when such mammal is predisposed to the disease-state but has not yetbeen diagnosed as having it; (b) modulating the disease-state, i.e.,arresting it development; and/or (c) relieving the disease-state, i.e.,causing regression of the disease state.

Synthesis

The compounds of the present invention can be prepared in a number ofways well known to one skilled in the art of organic synthesis. Thecompounds of the present invention can be synthesized using the methodsdescribed below, together with synthetic methods known in the art ofsynthetic organic chemistry, or variations thereon as appreciated bythose skilled in the art. Preferred methods include, but are not limitedto, those described below. All references cited herein are herebyincorporated in their entirety by reference.

The novel compounds of Formula I and IA may be prepared using thereactions and techniques described in this section. The reactions areperformed in solvents appropriate to the reagents and materials employedand are suitable for the transformations being effected. Also, in thedescription of the synthetic methods described below, it is to beunderstood that all proposed reaction conditions, including solvent,reaction atmosphere, reaction temperature, duration of the experimentand workup procedures, are chosen to be the conditions standard for thatreaction, which should be readily recognized by one skilled in the art.One skilled in the art of organic synthesis understands that thefunctionality present on various portions of the edict molecule must becompatible with the reagents and reactions proposed. Not all compoundsof Formula I and IA falling into a given class may be compatible withsome of the reaction conditions required in some of the methodsdescribed. Such restrictions to the substituents, which are compatiblewith the reaction conditions, will be readily apparent to one skilled inthe art and alternate methods must be used.

Compounds of Formula I and IA may be prepared by procedures depicted inScheme 1. Intermediate 1, obtained from commercial sources, can bereacted with R₁X (where R₁ other than H is as defined with respect toFormula I and IA and X is a halide) in the presence of a ligand such as8-hydroxyquinoline, CuI (I) and a base such as K₂CO₃ in a suitablesolvent such as DMF, DMSO etc. at an elevated temperature to yieldintermediate 2. Cleavage of the benzyl group of intermediate 2 can beperformed using the methods known in the art such as hydrogenolysiscatalyzed by palladium. Intermediate 3 can then be alkylated withintermediate 4, which can be prepared by reaction of the correspondingalcohols with methanesulfonyl chloride, in the presence of a base suchas K₂CO₃ at an elevated temperature. The above alcohols are commerciallyavailable or can be prepared by many methods well known to one skilledin the art (typical examples may be found in Sandler, S. et al., OrganicFunctional Group Preparations, Vol. I (Academic Press, Inc., 1983)).Removal of the protecting group of intermediate 5 can be carried outwith appropriate reagents well known to those skilled in the art (forspecific details see Greene et al., Protecting Groups in OrganicSynthesis (John Wiley & Sons Inc., 1991)). The deprotected product canthen be treated with R₂X (where R₂ is defined as in Formula I and IA andX is a leaving group such as halide, mesylate, triflate, etc.), whichare commercially available or can be prepared by many methods known inthe art, at a number of conditions that are routine for those skilled inthe art of organic synthesis to afford compounds of Formula I and IA.Alternatively the intermediate 6 can also be reacted with isocyates orisothiocyanates in the presence of a base such as Et₃N to provide thecompounds of Formula I and IA.

Compounds of Formula I and IA, wherein Y is defined as S, S(═O) or S(O)₂, may be prepared by procedures outlined in Scheme 2. Halogenationof intermediate 3 generated as described in Scheme I can be achievedwith POBr₃, PBr₃ or POCl₃ using the conditions known to one skilled inthe art. The halogenated pyridone can then be reacted with intermediate8, which can be prepared according to the procedures described in U.S.Pat. No. 6,556,384 B1 (Owen, D. et al.) incorporated by reference hereinas to these preparations, in the presence of a base such as NaH to yieldintermediate 9. Oxidation of intermediate 9 with an oxidant such asmCPBA in a suitable solvent such as CH₂Cl₂ affords intermediate 10 andintermediate 11. Intermediate 9, intermediate 10 or intermediate 11 canbe carried forward to compounds of Formula I and IA following theprocedures described above in Scheme 1 substituting intermediate 9, 10or 11 for intermediate 5.

Compounds of Formula I and IA, wherein Y is defined as NR₃, may beprepared by procedures illustrated in Scheme 3. Intermediate 7 preparedas described in Scheme II can be reacted with intermediate 12, which arecommercially available or can be prepared by the methods known to oneskilled in the art, in the presence of a catalyst such as Pd (P(tBu)₃)₂and a base such as NaOtBu in a suitable solvent such as toluene to yieldintermediate 13. The products can then be further elaborated tocompounds of Formula I and IA using the procedures described above inScheme 1 substituting intermediate 13 for intermediate 5.

Alternatively, compounds of Formula I and IA, wherein Y is defined as NR₃, may also be prepared by the procedures similar to those provided inScheme 3. Those invention compounds can be alternatively obtained bytreatment of the compounds of Formula I and IA, wherein R₃═H, with asuitable electrophile R₃X (where X is a halide, mesylate, triflate,etc.) in the presence of a base such as K₂CO₃, CsCO₃, NaOtBu, etc.

Alternatively, compounds of Formula I and IA can be synthesized byprocedures outlined in Scheme 4. Intermediate 14, obtained fromcommercial sources, can be reacted with intermediate 15, which arecommercially available or can be generated by many methods readilyrecognized by one skilled in the art (typical examples may be found inSandler, S. et al., Organic Functional Group Preparations, Vol. I(Academic Press, Inc., 1983)), in the presence of a base such as NaH toyield intermediate 16. Hydrolysis of intermediate 16 can be achieved bytreatment with DABCO in the presence of a base such as K₂CO₃ indioxane/water at an elevated temperature. Intermediate 17 can then bereacted with R₁X (where R₁ is defined with respect to Formula I or IAand X is a halide) in the presence of a ligand such as8-hydroxyquinoline, CuI (I) and a base such as K₂CO₃ in a suitablesolvent such as DMF, DMSO etc. at an elevated temperature to yieldintermediate 18. The intermediate 18 can be carried forward to compoundsof Formula I and IA following the procedures described above in Scheme 1substituting intermediate 18 for intermediate 5.

Compounds of Formula I and IA may be prepared by procedures illustratedin Scheme 5. Intermediate 3 generated as described in Scheme I can bereacted with intermediate 19, which are commercially available or can bemade by many methods readily recognized by one skilled in the art(typical examples may be found in Sandler, S. et al., Organic FunctionalGroup Preparations, Vol. I (Academic Press, Inc., 1983)), via Mitsunoboreaction to yield intermediate 20 which can be converted to Formula I orIA using the procedures described above in Scheme 1 substitutingintermediate 20 for intermediate 5.

Alternatively, compounds of Formula I and IA may be synthesized asprovided in Scheme 6. Intermediate 21, obtained from commercial sources,can be reacted with intermediate 4 prepared as described in Scheme Itogive intermediate 22. Hydrolysis of intermediate 22 can be achieved bytreatment with DABCO in the presence of a base such as K₂CO₃ indioxane/water at an elevated temperature. Intermediate 23 can be treatedwith R₁X (where R₁ is defined with respect to Formula I or IA and X is ahalide) in the presence of a ligand such as 8-hydroxyquinoline, CuI (I)and a base such as K₂CO₃ in a suitable solvent such as DMF, DMSO etc atan elevated temperature to yield intermediate 24. The intermediate 24can be carried forward to compounds of Formula I and IA following theprocedures described above in Scheme 1 substituting intermediate 24 forintermediate 5.

Compounds of Formula I and IA can also be prepared by proceduresillustrated in Scheme 7. Intermediate 25 (R₁—NH₂, where R₁ is as definedin Formula I and IA), which are commercially available or can be made bymethods recognized by one skilled in the art, can be converted toformamidine intermediate 26 in a two step procedure described byDonetti, A. et al. (J. Med. Chem., 27:380 (1984)). Intermediate 26 canbe reacted with dimethyl malonate to yield intermediate 27 usingliterature procedures (J. Med. Chem., 45:3639 (2002)). The intermediate27 can then be carried forward to compounds of Formula I and IAfollowing the procedures described above in Scheme 1 substitutingintermediate 28 for intermediate 3.

ABBREVIATIONS

The following abbreviations are employed in the Examples and elsewhereherein:

-   EtOAc=ethyl acetate-   DMF=dimethylformamide-   THF=tetrahydrofuran-   K₂CO₃=potassiumm carbonate-   Na₂CO₃=sodium carbonate-   MgSO₄=magnesium sulfate-   SiO₂=silicon dioxide-   CH₂Cl₂=methylene chloride-   MeOH=methanol-   HCl=hydrochloric acid-   Cs₂CO₃=cesium carbonate-   KOH=potassium hydroxide-   DME=1,2-dimethoxyethane-   Pd(dppf)Cl₂=[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium    (II)-   t-BuONa=sodium tert-butoxide-   Pd₂(dba)₃=tris(dibenzylideneacetone)dipalladium (0)-   TFA=trifluoroacetic acid-   BINAP=rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl-   DABCO=1,4-diazabicyclo[2.2.2]octane-   mCPBA=m-chloroperoxybenzoic acid-   min=minute(s)-   h or hr=hour(s)-   mL or ml=milliliter-   g=gram(s)-   mg=milligram(s)-   mmol=millimole(s)-   LRMS=low resolution mass spectrometry-   NMR=nuclear magnetic resonance

EXAMPLES

The following Examples are offered as illustrative as a partial scopeand particular embodiments of the invention and are not meant to belimiting of the scope of the invention. Abbreviations and chemicalsymbols have their usual and customary meanings unless otherwiseindicated. Unless otherwise indicated, the compounds described hereinhave been prepared, isolated and characterized using the Schemes andother methods disclosed herein or may be prepared using same.

Example 1 Preparation of tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Step A. Preparation of4-(benzyloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

A mixture of 4-benzyloxy-2(1H)-pyridone (6.87 g, 34.1 mmol, Aldrich),4-bromophenyl methyl sulphone (8.01 g, 34.1 mmol, Combi-Blocks Inc.),copper(I) iodide (1.30 g, 6.82 mmol, Aldrich), 8-hydroxyquinoline (0.99g, 6.82 mmol, Alfa Aesar) and potassium carbonate (6.12 g, 44.3 mmol,EMD) in DMSO (100 mL) was heated at 145° C. for 6 h, cooled to roomtemperature and then diluted with 10% NH₄OH aqueous solution (50 mL) andEtOAc (100 mL). The resulting mixture was filtered and the solid waswashed with H₂O and EtOAc to give 8.0 g crude product as a greenishsolid. MS (ESI) 356 (M+H).

Step B. Preparation of 4-hydroxy-1-(4-(methylsulfonyl)_(p) henyl)pyridin-2 (1H)-one

A stirring suspension of4-(benzyloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one (3.0 g, 8.44mmol) and palladium on activated carbon (1.63 g, 10 wt. %, wet, Aldrich)in THF (150 mL) and methanol (250 mL) was placed under hydrogen(balloon) for 1 h. The resulting mixture was purged with nitrogen andthen diluted with THF (150 mL) and methanol (50 mL). After stirringunder nitrogen for 30 min, the mixture was filtered through a pad ofCELITE® 545 filter aid and the filtrate was evaporated under reducedpressure to give 2.28 g crude product as a dark greenish solid. MS (ESI)266 (M+H).

Step C. Preparation of tert-butyl4-(methylsulfonyloxy)piperidine-1-carboxylate

To a stirring solution of tert-butyl-4-hydroxy-1-piperidinecarboxylate(10.28 g, 51.08 mmol, Aldrich) and Et₃N (14.25 mL, 102.16 mmol, EMD) inCH₂Cl₂ (300 mL) at room temperature was added methanesulfonyl chloride(4.35 mL, 56.19 mmol, Aldrich) dropwise. The reaction mixture wasstirred at room temperature for 4 h and washed with 0.1N HCl aqueoussolution, H₂O and brine. The organic layer was dried with Na₂SO₄ andconcentrate in vacuo to yield 14.3 g of the crude product as a lightorange solid.

Step D Example 1

A stirring mixture of4-hydroxy-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one (2.27 g, 8.55mmol), tert-butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate (3.6 g,12.83 mmol) and potassium carbonate (2.36 g, 17.1 mmol, EMD) in DMF (50mL) was heated at 90° C. overnight and then cooled to room temperature.The resulting mixture was diluted with EtOAc and H₂O and the aqueouslayer was extracted further with EtOAc (2×). The combined extracts werewashed with H₂O/brine (1:1, 3×), dried (Na₂SO₄) and evaporated. Theresidual was purified by flash chromatography (0 to 10% MeOH/CH₂Cl₂) toyield 2.57 g (67%) of Example 1 as a yellow solid. ¹H NMR (500 MHz,CDCl₃) δ 8.07 (d, J=8.80 Hz, 2H), 7.62 (d, J=8.80 Hz, 2H), 7.23 (d,J=7.70 Hz, 1H), 6.06 (dd, J=7.42, 2.47 Hz, 1H), 5.97 (d, J=2.75 Hz, 1H),4.38-4.57 (m, 1H), 3.63-3.78 (m, 2H), 3.22-3.45 (m, 2H), 3.09 (s, 3H),1.93-2.03 (m, 2H), 1.69-1.85 (m, 2H), 1.48 (s, 9H). MS (ESI) 449 (M+H).

Example 2 Preparation of 1,1,1-trifluoropropan-2-yl4-(1-(2-fluoro-4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Step A. Preparation of1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloric acid salt

A mixture of tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(2.515 g, 5.61 mmol) and hydrogen chloride (4.0 M in dioxane, 35.0 mL,Aldrich) in methanol (45 mL) was stirred for 1 h and then concentratedin vacuo. The obtained solid was dissolved in methanol and evaporated togive 2.28 g of the crude product as a dark yellow solid. MS (ESI) 349(M+H).

Step B. Preparation of 1,1,1-trifluoropropan-2-yl chloroformate

To a mixture of 1,1,1-trifluoro-2-propanol (114.1 mg, 1.0 mmol, MatrixScientific) and triphosgene (98 mg, 0.33 mmol, Aldrich) in ethyl ether(10 mL) at −40° C. was added pyridine (80 μL, 1.0 mmol, EMD) in ethylether (1.0 mL) dropwise. The reaction mixture was warmed to 0° C. andstirred for 6 h. The flask containing the above reaction mixture was putinto a refrigerator overnight and then filtered. The filtrate wasconcentrated in vacuo in ice both to colorless oil which was useddirectly in the next step.

Step C Example 2

To a suspension of1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloric acid salt (30.8 mg, 0.08 mmol) in CH₂Cl₂ was addeddiisopropylethylamin (70 μL, 0.40 mmol, Aldrich) followed by addition of1,1,1-trifluoropropan-2-yl chloroformate (⅓ of the material from Step B,0.33 mmol) in CH₂Cl₂ (0.5 mL). The reaction mixture was stirred for 30min and then evaporated under the reduced pressure to yield the crudeproduct which was purified by preparative HPLC (C₁₈ column; 10-100%acetonitrile in water containing 0.05% trifluoroacetic acid) to giveExample 2 (16.8 mg, off-white solid, 43%) upon lyophilization. ¹H NMR(500 MHz, CDCl₃) δ 8.07 (d, J=8.80 Hz, 2H), 7.59 (d, J=8.80 Hz, 2H),7.25 (d, J=7.70, 1H), 6.03-6.22 (m, 2H), 5.17-5.36 (m, 1H), 4.57 (m,1H), 3.64-3.85 (m, 2H), 3.37-3.56 (m, 2H), 3.10 (s, 3H), 1.95-2.08 (m,2H), 1.76-1.93 (m, 2H), 1.42 (d, J=6.60 Hz, 3H). MS (ESI) 489 (M+H).

Example 3 Preparation of isopropyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

To a solution of tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(53 mg, 0.118 mmol) in CH₂Cl₂ (1.0 mL) was added TFA (0.5 mL) dropwise.The reaction mixture was stirred for 1 h and evaporated under reducedpressure. The residue was then dissolved in CH₂Cl₂ (1.5 mL) followed byaddition of Et₃N (82 μL, 0.59 mmol) and isopropyl chloroformate (0.295mL, 0.295 mmol, Aldrich). The resulting mixture was stirred at roomtemperature for 30 min, quenched with H₂O (0.2 mL) and then evaporatedto dryness. The crude product was purified by preparative HPLC (C₁₈column; 10-100% methanol in water containing 0.05% trifluoroacetic acid)to give Example 3 (44.5 mg, white solid, 87%) upon lyophilization. ¹HNMR (500 MHz, CDCl₃) δ 8.09 (d, J=8.80 Hz, 2H), 7.61 (d, J=8.25 Hz, 2H),7.30 (d, J=7.70 Hz, 1H), 6.28 (d, J=2.20 Hz, 1 H), 6.19 (dd, J=7.70,2.20 Hz, 1H), 4.86-5.00 (m, 1H), 4.51-4.63 (m, 1H), 3.77 (app brs, 2H),3.33-3.44 (m, 2H), 3.11 (s, 3H), 1.96-2.11 (m, 2H), 1.73-1.86 (m, J=7.15Hz, 2H), 1.26 (d, J=6.05 Hz, 6H). MS (ESI) 435 (M+H).

Example 4 Preparation of tert-butyl4-((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)methyl)piperidine-1-carboxylate

To a stirring solution of triphenylphosphine (86.6 mg, 0.33 mmol,Aldrich) in THF (1.5 mL) was added4-hydroxy-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one (39.8 mg, 0.15mmol), N-Boc-4-piperidinemethanol (71.0 mg, 0.33 mmol, Aldrich) anddiisopropylazodicarboxylate (63.9 μL, 0.33 mmol, Aldrich). The reactionmixture was stirred for 1.5 h, quenched with methanol (1.5 mL) and thenevaporated under reduced pressure. The residue was purified by flashchromatography (0-100% EtOAc/Hexanes) to give 33 mg (48%) of Example 4as a white solid. ¹H NMR (500 MHz, CDCl₃) δ 8.06 (d, J=8.80 Hz, 2H),7.61 (d, J=8.80 Hz, 2H), 7.22 (d, J=7.70 Hz, 1H), 6.06 (dd, J=7.70, 2.75Hz, 1H), 5.94 (d, J=2.20 Hz, 1H), 4.18 (app brs, 2H), 3.83 (d, J=6.05Hz, 2H), 3.09 (s, 3H), 2.75 (app brs, 2H), 1.91-2.09 (m, 1H), 1.71-1.85(m, 2H), 1.47 (s, 9H), 1.19-1.38 (m, 2H). MS (ESI) 464 (M+H).

Example 5 Preparation of isopropyl4-((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)methyl)piperidine-1-carboxylate

Example 5 was prepared according to procedures described in Example 3substituting tert-butyl4-((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)methyl)piperidine-1-carboxylatefor tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate.¹H NMR (500 MHz, CDCl₃) δ 8.07 (d, J=8.25 Hz, 2H), 7.61 (d, J=8.80 Hz,2H), 7.23 (d, J=7.70 Hz, 1H), 6.09 (dd, J=7.70, 2.75 Hz, 1H), 6.01 (d,J=2.75 Hz, 1H), 4.87-4.98 (m, 1H), 4.23 (app brs, 2H), 3.85 (d, J=6.05Hz, 2H), 3.09 (s, 3H), 2.79 (t, J=12.65 Hz, 2H), 1.87-2.06 (m, 1H),1.76-1.87 (d, J=12.10 Hz, 2H), 1.18-1.37 (m, 6H), 1.25 (d, J=6.05 Hz,6H). MS (ESI) 449 (M+H).

Example 6 Preparation of tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)azepane-1-carboxylate

Example 6 was prepared according to procedures described in Example 1substituting tert-butyl 4-hydroxyazepane-1-carboxylate (SynChem, Inc.)for tert-butyl-4-hydroxy-1-piperidinecarboxylate in Step C. ¹H NMR (500MHz, CDCl₃) δ 8.07 (d, J=8.80 Hz, 2H), 7.61 (d, J=8.80 Hz, 2H), 7.22 (d,J=7.70 Hz, 1H), 6.03 (d, J=7.70 Hz, 1H), 5.91 (s, 1H), 4.40-4.51 (m,1H), 3.32-3.60 (m, 4H), 3.09 (s, 3H), 2.06-2.17 (m, 1H), 1.87-2.03 (m,4H), 1.63-1.73 (m, 1H), 1.48 (s, 9H). MS (ESI) 463 (M+H).

Example 7 Preparation of isopropyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)azepane-1-carboxylate

Example 7 was prepared according to procedures described in Example 3substituting tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)azepane-1-carboxylatefor tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate.¹H NMR (500 MHz, CDCl₃) δ 8.08 (d, J=8.80 Hz, 2H), 7.61 (d, J=8.80 Hz,2H), 7.29 (d, J=7.70 Hz, 1H), 6.22 (s, 1H), 6.17 (d, J=7.70 Hz, 1H),4.90-5.02 (m, 1H), 4.48-4.56 (m, 1H), 3.36-3.63 (m, 4H), 3.11 (s, 3H),1.91-2.17 (m, 5H), 1.64-1.77 (m, 1H), 1.27 (d, J=6.05 Hz, 6H). MS (ESI)449 (M+H).

Example 8 Preparation of isopropyl4-(1-(4-cyanophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Step A. Preparation of 4-hydroxypyridin-2(1H)-one

A stirring mixture of 4-benzyloxy-2(1H)-pyridine (5.0 g, 24.85 mmol,Aldrich) and palladium on activated carbon (2.6 g, 10 wt. %, wet,Aldrich) in methanol (200 mL) was under hydrogen (balloon) for 2 h. Theresulting mixture was purged with nitrogen and then diluted withmethanol (50 mL) and CH₂Cl₂ (10 mL). After stirring under nitrogen for30 min, the mixture was filtered through a pad of CELITE® 545 filter aidand the filtrate was evaporated under reduced pressure to give 2.73 gcrude product as a light orange solid.

Step B. Preparation of isopropyl4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

A stirring mixture of 4-hydroxypyridin-2(1H)-one (1.5 g, 13.5 mmol),isopropyl 4-(methylsulfonyloxy)piperidine-1-carboxylate (5.0 g, 18.9mmol, prepared according to the procedure described in Step C ofExample 1) and potassium carbonate (3.7 g, 27.0 mmol, EMD) in DMF (80mL) was heated at 140° C. for 2 h and then cooled to room temperature.The resulting mixture was diluted with EtOAc and H₂O and the aqueouslayer was extracted further with EtOAc (7×). The combined extracts werewashed with saturated NH₄Cl aqueous solution (2×), dried (Na₂SO₄) andevaporated. The residual was purified by flash chromatography (0 to 100%EtOAc/Hexanes and then 5% MeOH/CH₂Cl₂) to yield 1.67 g (44%) of theproduct as an off-white solid. MS (ESI) 281 (M+H).

Step C Example 8

A mixture of isopropyl4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (42 mg,0.15 mmol,), 4-bromobenzonitrile (27.3 mg, 0.15 mmol, Aldrich.),copper(I) iodide (5.7 mg, 0.03 mmol, Aldrich), 8-hydroxyquinoline (4.4mg, 0.03 mmol, Alfa Aesar) and potassium carbonate (26.9 mg, 0.195 mmol,EMD) in DMSO (0.6 mL) was heated under Microwave conditions (160° C., 30min), then cooled to room temperature and finally purified bypreparative HPLC (C₁₈ column; 0-100% methanol in water containing 0.05%trifluoroacetic acid) to give Example 8 (23.1 mg, off-white solid, 40%)upon lyophilization. ¹H NMR (500 MHz, CDCl₃) δ 7.79 (d, J=8.80 Hz, 2H),7.53 (d, J=8.80 Hz, 2H), 7.21 (d, J=7.70 Hz, 1H), 6.04 (dd, J=7.70, 2.75Hz, 1H), 5.96 (d, J=2.75 Hz, 1H), 4.89-4.99 (m, 1H), 4.44-4.55 (m, 1H),3.70-3.80 (m, 2H), 3.33-3.43 (m, 2H), 1.93-2.05 (m, 2H), 1.72-1.85 (m, 2H), 1.26 (d, J=6.05 Hz, 6H). MS (ESI) 382 (M+H).

Example 9 Preparation of isopropyl4-(1-(2-fluoro-4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 9 was prepared according to procedures described in Example 8substituting 1-bromo-2-fluoro-4-(methylsulfonyl)benzene (preparedaccording to procedures described in International Patent ApplicationNo. WO 2004/089885) for 4-bromobenzonitrile in Step C except that thereaction was heated at 180° C. in a microwave for 1 h. ¹H NMR (500 MHz,CDCl₃) δ 7.84-7.89 (m, 2H), 7.62 (t, J=7.70 Hz, 1H), 7.17 (d, J=7.70 Hz,1H), 6.11-6.20 (m, 2H), 4.88-5.01 (m, 1H), 4.47-4.61 (m, 1H), 3.70-3.83(m, 2H), 3.35-3.48 (m, 2H), 3.12 (s, 3H), 1.96-2.06 (m, 2 H), 1.73-1.86(m, 2H), 1.26 (d, J=6.60 Hz, 6H). MS (ESI) 453 (M+H).

Example 10 Preparation of isopropyl4-(1-(4-methoxyphenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 10 was prepared according to procedures described in Example 8substituting 1-bromo-4-methoxybenzene for 4-bromobenzonitrile in Step C.¹H NMR (500 MHz, CD₃OD). 7.50 (d, J=7.70 Hz, 1H), 7.26 (d, J=8.80 Hz,2H), 7.04 (d, J=8.80 Hz, 2H), 6.21 (dd, J=7.70, 2.75 Hz, 1H), 6.04 (d,J=2.75 Hz, 1H), 4.82-4.92 (m, 1H), 4.64-4.74 (m, 1H), 3.84 (s, 3H),3.69-3.80 (m, 2H), 3.36-3.45 (m, 2H), 1.96-2.07 (m, 2H), 1.68-1.79 (m,2H), 1.26 (d, J=6.05 Hz, 6H). MS (ESI) 387 (M+H).

Example 11 Preparation of isopropyl4-(1-(3-cyanophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 11 was prepared according to procedures described in Example 8substituting 3-bromobenzonitrile for 4-bromobenzonitrile in Step C. ¹HNMR (500 MHz, CDCl₃) δ 7.56-7.81 (m, 4H), 7.26 (d, J=7.70 Hz, 1H), 6.26(d, J=2.75 Hz, 1 H), 6.16 (dd, J=7.70, 2.75 Hz, 1H), 4.89-5.05 (m, 1H),4.50-4.62 (m, 1H), 3.77 (app brs, 2H), 3.33-3.47 (m, 2H), 1.93-2.09 (m,2H), 1.74-1.85 (m, 2H), 1.26 (d, J=6.05 Hz, 6H). MS (ESI) 382 (M+H).

Example 12 Preparation of isopropyl4-(1-(3-methoxyphenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 12 was prepared according to procedures described in Example 8substituting 1-bromo-3-methoxybenzene for 4-bromobenzonitrile in Step C.¹H NMR (500 MHz, CDCl₃) δ 7.39 (t, J=7.97 Hz, 1H), 7.33 (d, J=7.70 Hz,1H), 6.98 (dd, J=8.25, 2.20 Hz, 1H), 6.91 (d, J=8.25 Hz, 1H), 6.89 (t,J=2.20 Hz, 1H), 6.41 (d, J=2.20 Hz, 1H), 6.16 (dd, J=7.70, 2.75 Hz, 1H),4.89-4.98 (m, 1H), 4.51-4.60 (m, 1H), 3.83 (s, 3H), 3.77 (app brs, 2H),3.33-3.44 (m, 2H), 1.96-2.06 (m, 2H), 1.79 (app brs, 2H), 1.26 (d,J=6.05 Hz, 6H). MS (ESI) 387 (M+H).

Example 13 Preparation of isopropyl4-(2-oxo-1-(4-(trifluoromethyl)phenyl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 13 was prepared according to procedures described in Example 8substituting 1-bromo-4-(trifluoromethyl)benzene for 4-bromobenzonitrilein Step C. ¹H NMR (500 MHz, CDCl₃) δ 7.76 (d, J=8.25 Hz, 2H), 7.52 (d,J=8.25 Hz, 2H), 7.25 (d, J=7.1 Hz, 1H), 6.01-6.17 (m, 2H), 4.83-5.03 (m,1H), 4.44-4.59 (m, 1 H), 3.76 (app brs, 2H), 3.29-3.47 (m, 2H),1.90-2.11 (m, 2H), 1.80 (app brs, 2H), 1.26 (d, J=6.05 Hz, 6H).). MS(ESI) 425 (M+H).

Example 14 Preparation of isopropyl4-(1-(3-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 14 was prepared according to procedures described in Example 8substituting 1-bromo-3-(methylsulfonyl)benzene (available from OakwoodProduct Inc.) for 4-bromobenzonitrile in Step C. ¹H NMR (500 MHz, CDCl₃)δ 8.01 (m, 1H), 7.95 (s, 1H), 7.72 (m, 2H), 7.30 (d, J=7.70 Hz, 1H),6.11-6.23 (m, 2H), 4.88-5.02 (m, 1H), 4.47-4.62 (m, 1H), 3.72-3.82 (m,2H), 3.31-3.47 (m, 2H), 3.11 (s, 3H), 1.95-2.08 (m, 2H), 1.81 (app brs,2H), 1.26 (d, J=6.60 Hz, 6H). MS (ESI) 435 (M+H).

Example 15 Preparation of isopropyl4-(2-oxo-1-(pyridin-4-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate,TFA salt

Example 15 was prepared according to procedures described in Example 8substituting 4-bromopyridine hydrochloride for 4-bromobenzonitrile inStep C. ¹H NMR (500 MHz, CDCl₃) 14.50 (brs, 2H), 8.34 (brs, 2H), δ 7.32(d, J=7.15 Hz, 1H), 6.18 (d, J=7.15 Hz, 1H), 6.06 (s, 1H), 4.88-4.99 (m,1H), 4.53 (app brs, 1H), 3.76 (app brs, 2H), 3.34-3.44 (m, 2H), 2.00(app brs, 2H), 1.80 (app brs, 2H), 1.26 (d, J=6.05 Hz, 6H). MS (ESI) 358(M+H).

Example 16 Preparation of isopropyl4-(2-oxo-1-(pyridin-3-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 16 was prepared according to procedures described in Example 8substituting 3-bromopyridine for 4-bromobenzonitrile in Step C. ¹H NMR(500 MHz, CDCl₃) δ 8.74 (brs, 2H), 8.08 (d, J=8.25 Hz, 1H), 7.69 (brs,1H), 7.29 (d, J=8.25 Hz, 1H), 6.13-6.18 (m, 2H), 4.88-5.01 (m, 1H),4.46-4.62 (m, 1H), 3.70-3.83 (m, 2H), 3.31-3.46 (m, 2H), 1.93-2.07 (m,2H), 1.74-1.86 (m, 2H), 1.26 (d, J=6.60 Hz, 6H). MS (ESI) 358 (M+H).

Example 17 Preparation of tert-butyl3-((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)methyl)pyrrolidine-1-carboxylate

Example 17 was prepared according to procedures described in Example 1substituting tert-butyl 3-(hydroxymethyl)pyrrolidine-1-carboxylate fortert-butyl 4-hydroxy-1-piperidinecarboxylate in Step C. ¹H NMR (500 MHz,CDCl₃) δ 8.07 (d, J=8.25 Hz, 2H), 7.61 (d, J=8.80 Hz, 2H), 7.22 (d,J=7.70 Hz, 1H), 6.02-6.11 (m, 1 H), 5.95 (d, J=2.75 Hz, 1H), 3.86-4.02(m, 2H), 3.32-3.67 (m, 3H), 3.12-3.30 (m, 1H), 3.09 (s, 3H), 2.65-2.75(m, 1H), 2.03-2.15 (m, 1H), 1.72-1.83 (m, 1H), 1.48 (s, 9H). MS (ESI)449 (M+H).

Example 18 Preparation of 4-chlorophenyl3-((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)methyl)pyrrolidine-1-carboxylate

Example 18 was prepared according to procedures described in Example 2,Step A and Step C, substituting tert-butyl3-((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)methyl)pyrrolidine-1-carboxylatefor tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatein Step A and 4-chlorophenyl chloroformate for1,1,1-trifluoropropan-2-yl chloroformate in Step C. ¹H NMR (500 MHz,CDCl₃) δ 8.07 (d, J=8.25 Hz, 2H), 7.61 (d, J=8.25 Hz, 2H), 7.32 (d,J=8.80 Hz, 2H), 7.25 (dd, J=7.70, 3.30 Hz, 1H), 7.09 (d, J=8.80 Hz, 2H),6.06-6.12 (m, 1H), 5.98-6.03 (m, 1H), 3.92-4.09 (m, 2H), 3.49-3.92 (m,3H), 3.34-3.48 (m, 1H), 3.09 (s, 3H), 2.73-2.89 (m, 1H), 2.12-2.29 (m,1H), 1.79-1.97 (m, 1H). MS (ESI) 503 (M+H).

Example 19 Preparation of 2-chlorophenyl3-((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)methyl)pyrrolidine-1-carboxylate

Example 19 was prepared according to procedures described in Example 2,Step A and Step C, substituting tert-butyl3-((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)methyl)pyrrolidine-1-carboxylatefor tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatein Step A and 2-chlorophenyl chloroformate for1,1,1-trifluoropropan-2-yl chloroformate in Step C. ¹H NMR (500 MHz,CDCl₃) δ 8.08 (d, J=8.80 Hz, 2H), 7.61 (d, J=8.80 Hz, 2H), 7.43 (d,J=8.25 Hz, 1H), 7.23-7.31 (m, 3H), 7.14-7.19 (m, 1H), 6.10-6.21 (m, 2H),3.38-4.14 (m, 6H), 3.10 (s, 3H), 2.77-2.93 (m, 1 H), 2.15-2.32 (m, 1H),1.83-2.00 (m, 1H). MS (ESI) 503 (M+H).

Example 20 Preparation of tert-butyl3-((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)methyl)azetidine-1-carboxylate

Example 20 was prepared according to procedures described in Example 1substituting tert-butyl 3-(hydroxymethyl)azetidine-1-carboxylate fortert-butyl 4-hydroxy-1-piperidinecarboxylate in Step C. ¹H NMR (500 MHz,CDCl₃) δ 8.07 (d, J=8.80 Hz, 2H), 7.62 (d, J=8.80 Hz, 2H), 7.23 (d,J=7.70 Hz, 1H), 6.07 (dd, J=7.70, 2.75 Hz, 1H), 5.97 (d, J=2.75 Hz, 1H),4.06-4.14 (m, 4H), 3.79 (dd, J=8.80, 4.95 Hz, 2H), 3.09 (s, 3H),2.94-3.05 (m, 1H), 1.46 (s, 9H). MS (ESI) 435 (M+H).

Example 21 Preparation of 4-chlorophenyl3-((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)methyl)azetidine-1-carboxylate

Example 21 was prepared according to procedures described in Example 2,Step A and Step C, substituting tert-butyl3-((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)methyl)azetidine-1-carboxylatefor tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatein Step A and 4-chlorophenyl chloroformate for1,1,1-trifluoropropan-2-yl chloroformate in Step C. ¹H NMR (500 MHz,CDCl₃) δ 8.09 (d, J=8.25 Hz, 2H), 7.62 (d, J=8.80 Hz, 2H), 7.29-7.36 (m,3H), 7.05-7.12 (m, 2H), 6.16-6.25 (m, 2 H), 4.38 (app br. s, 1H), 4.28(app br. s, 1H), 4.21 (d, J=6.05 Hz, 2H), 4.09 (app br. s, 1H), 4.00(app br. s, 1H), 3.14-3.23 (m, 1H), 3.11 (s, 3H). MS (ESI) 489 (M+H).

Example 22 Preparation of 2-chlorophenyl3-((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)methyl)azetidine-1-carboxylate

Example 22 was prepared according to procedures described in Example 2,Step A and Step C, substituting tert-butyl3-((1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)methyl)azetidine-1-carboxylatefor tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatein Step A and 2-chlorophenyl chloroformate for1,1,1-trifluoropropan-2-yl chloroformate in Step C. ¹H NMR (500 MHz,CDCl₃) δ 8.09 (d, J=8.25 Hz, 2H), 7.62 (d, J=8.25 Hz, 2H), 7.43 (dd,J=7.97, 1.37 Hz, 1H), 7.32 (d, J=7.70 Hz, 1H), 7.16-7.31 (m, 3H), 6.28(d, J=2.20 Hz, 1H), 6.25 (dd, J=7.70, 2.75 Hz, 1H), 4.41 (app brs, 1H),4.31 (app brs, 1H), 4.23 (d, J=6.05 Hz, 2H), 4.20 (app brs, 1H), 4.04(app brs, 1H) 3.15-3.26 (m, 1H), 3.11 (s, 3H). MS (ESI) 489 (M+H).

Example 23 Preparation of 1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 23 was prepared according to procedures described in Example 2substituting 1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-ol for1,1,1-trifluoro-2-propanol in Step B. ¹H NMR (500 MHz, CDCl₃) δ 8.08 (d,J=8.80 Hz, 2H), 7.62 (d, J=8.80 Hz, 2H), 7.26 (d, J=7.70 Hz, 1H), 6.50(s, 1H), 6.09 (dd, J=7.70, 2.75 Hz, 1 H), 6.02 (d, J=2.75 Hz, 1H),4.55-4.63 (m, 1H), 3.91 (s, 3H), 3.82-3.92 (m, 1H), 3.73-3.83 (m, 1H),3.63-3.73 (m, 1H), 3.54-3.63 (m, 1H), 3.10 (s, 3H), 2.01-2.12 (m, 2H),1.86-1.98 (m, 2H). MS (ESI) 489 (M+H).

Example 24 Preparation of (3-exo)-tert-butyl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Example 24 was prepared according to procedures described in Example 1substituting (3-endo)-tert-butyl3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate for tert-butyl4-hydroxy-1-piperidinecarboxylate in Step C. ¹H NMR (500 MHz, CDCl₃) δ8.07 (d, J=8.80 Hz, 2H), 7.61 (d, J=8.80 Hz, 2H), 7.20 (d, J=7.70 Hz, 1H), 5.97-6.02 (m, 2H), 4.66-4.81 (m, 1H), 4.37 (app brs, 1H), 4.28 (appbrs, 1H), 3.09 (s, 3H), 1.99-2.19 (m, 4H), 1.65-1.90 (m, 4H), 1.49 (s,9H). MS (ESI) 475 (M+H).

Example 25 Preparation of (3-endo)-tert-butyl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Example 25 was prepared according to procedures described in Example 1substituting (3-exo)-tert-butyl3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate for tert-butyl4-hydroxy-1-piperidinecarboxylate in Step C. ¹H NMR (500 MHz, CDCl₃) δ8.07 (d, J=8.25 Hz, 2H), 7.61 (d, J=8.25 Hz, 2H), 7.24 (d, J=7.70 Hz,1H), 6.03 (dd, J=7.70, 2.75 Hz, 1H), 5.85 (d, J=2.20 Hz, 1H), 4.62 (t,J=4.40 Hz, 1H), 4.29 (app brs, 1H), 4.21 (app brs, 1H), 3.09 (s, 3H),1.92-2.29 (m, 8H), 1.48 (s, 9H). MS (ESI) 475 (M+H).

Example 26 Preparation of (3-exo)-isopropyl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Example 26 was prepared according to procedures described in Example 3substituting (3-exo)-tert-butyl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylatefor tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate.¹H NMR (500 MHz, CDCl₃) δ 8.07 (d, J=8.25 Hz, 2H), 7.61 (d, J=8.80 Hz,2H), 7.22 (d, J=7.70 Hz, 1H), 6.06 (d, J=2.75 Hz, 1H), 6.03 (dd, J=7.70,2.75 Hz, 1H), 4.91-5.03 (m, 1H), 4.70-4.81 (m, 1H), 4.41 (app brs, 1H),4.36 (app brs, 1H), 3.10 (s, 3H), 1.99-2.23 (m, 4H), 1.66-1.92 (m, 4H),1.27 (d, J=6.05 Hz, 6H). MS (ESI) 461 (M+H).

Example 27 Preparation of (3-endo)-isopropyl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Example 27 was prepared according to procedures described in Example 3substituting (3-endo)-tert-butyl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylatefor tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate.¹H NMR (500 MHz, CDCl₃) δ 8.08 (d, J=8.25 Hz, 2H), 7.61 (d, J=8.80 Hz,2H), 7.26 (d, J=7.70 Hz, 1H), 6.09 (dd, J=7.70, 2.75 Hz, 1H), 5.97 (d,J=2.75 Hz, 1H), 4.92-5.00 (m, 1H), 4.63 (t, J=4.67 Hz, 1H), 4.30 (appbrs, 2H), 3.10 (s, 3 H), 1.96-2.35 (m, 8H), 11.27 (d, J=6.60 Hz, 6H). MS(ESI) 461 (M+H).

Example 28 Preparation of(3-exo)-1-(4-(methylsulfonyl)phenyl)-4-(8-(pyrimidin-2-yl)-8-azabicyclo[3.2.1]octan-3-yloxy)pyridin-2(1H)-one,TFA salt

Step A. Preparation of(3-exo)-4-(8-azabicyclo[3.2.1]octan-3-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-onehydrochloric acid salt

(3-Exo)-4-(8-azabicyclo[3.2.1]octan-3-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-onehydrochloric acid salt was prepared according to procedures described inExample 2, Step A, substituting (3-exo)-tert-butyl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylatefor tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate.MS (ESI) 375 (M+H).

Step B Example 28

A mixture of(3-exo)-4-(8-azabicyclo[3.2.1]octan-3-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-onehydrochloric acid salt (41 mg, 0.10 mmol,), 2-bromopyrimidine (31.8 mg,0.20 mmol, Alfa Aesar) and potassium carbonate (55.2 mg, 0.40 mmol, EMD)in DMF (0.8 mL) was under Microwave conditions (160° C., 30 min) andthen cooled to room temperature. The reaction mixture was purified bypreparative HPLC (C₁₈ column; 0-100% methanol in water containing 0.05%trifluoroacetic acid) to give Example 28 (17.0 mg, yellow solid, TFAsalt, 30%) upon lyophilization. ¹H NMR (500 MHz, CDCl₃) δ 8.53 (d,J=4.95 Hz, 2H), 8.08 (d, J=8.80 Hz, 2H), 7.60 (d, J=8.25 Hz, 2H), 7.23(d, J=7.70 Hz, 1 H), 6.70 (t, J=5.22 Hz, 1H), 6.25 (d, J=2.20 Hz, 1H),6.03 (dd, J=7.70, 2.75 Hz, 1 H), 4.98 (m, 2H), 4.86-4.97 (m, 1H), 3.10(s, 3H), 2.26-2.40 (m, 2H), 2.14-2.27 (m, 2H), 1.92-2.03 (m, 2H),1.79-1.92 (m, 2H). MS (ESI) 461 (M+H).

Example 29 Preparation of(3-exo)-4-(8-(5-ethylpyrimidin-2-yl)-8-azabicyclo[3.2.1]octan-3-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one.TFA salt

Example 29 was prepared according to procedures described in Example 28substituting 2-chloro-5-ethylpyrimidine for 2-bromopyrimidine in Step Bexcept that the reaction was heated in a microwave at 160° C. for 1 h.¹H NMR (500 MHz, CDCl₃) δ 8.35 (s, 2H), 8.07 (d, J=8.80 Hz, 2H), 7.61(d, J=8.25 Hz, 2H), 7.19 (d, J=7.70 Hz, 1H), 6.07 (d, J=2.20 Hz, 1H),5.96 (dd, J=7.70, 2.75 Hz, 1H), 4.81-4.97 (m, 2H), 3.09 (s, 3H), 2.54(q, J=7.33 Hz, 2H), 2.14-2.30 (m, 4H), 1.78-1.98 (m, 4H), 1.24 (t,J=7.70 Hz, 3H). MS (ESI) 481 (M+H).

Example 30 Preparation of (3-exo)-cyclopentyl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Example 30 was prepared according to procedures described in Example 2,Step C, substituting(3-exo)-4-(8-azabicyclo[3.2.1]octan-3-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-onehydrochloric acid salt for1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloric acid salt and cyclopentyl chloroformate for1,1,1-trifluoropropan-2-yl chloroformate. ¹H NMR (500 MHz, CDCl₃) δ 8.08(d, J=8.80 Hz, 2H), 7.61 (d, J=8.80 Hz, 2H), 7.26 (d, J=7.70 Hz, 1H),6.25 (d, J=2.75 Hz, 1H), 6.10 (dd, J=7.70, 2.75 Hz, 1H), 5.15-5.19 (m,1H), 4.71-4.83 (m, 1H), 4.42 (app brs, 1H), 4.32 (app brs, 1H), 3.10 (s,3 H), 2.03-2.21 (m, 4H), 1.51-1.94 (m, 12H). MS (ESI) 487 (M+H).

Example 31 Preparation of (3-exo)-4-chlorophenyl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Example 31 was prepared according to procedures described in Example 2,Step C, substituting(3-exo)-4-(8-azabicyclo[3.2.1]octan-3-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-onehydrochloric acid salt for1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloric acid salt and 4-chlorophenyl chloroformate for1,1,1-trifluoropropan-2-yl chloroformate. ¹H NMR (500 MHz, CDCl₃) δ 8.08(d, J=8.80 Hz, 2H), 7.62 (d, J=8.25 Hz, 2H), 7.34 (d, J=8.80 Hz, 2H),7.22 (d, J=7.15 Hz, 1H), 7.10 (d, J=8.80 Hz, 2H), 5.98-6.06 (m, 2H),4.75-4.85 (m, 1H), 4.58 (app brs, 1H), 4.51 (app brs, 1H), 3.10 (s, 3H), 2.08-2.36 (m, 4H), 1.77-2.00 (m, 4H). MS (ESI) 529 (M+H).

Example 32 Preparation of (3-exo)-1,1,1-trifluoro-2-methylpropan-2-yl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Example 32 was prepared according to procedures described in Example 2,Step B-C, substituting 2-(trifluoromethyl)propan-2-ol for1,1,1-trifluoro-2-propanol in Step B and(3-exo)-4-(8-azabicyclo[3.2.1]octan-3-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-onehydrochloric acid salt for1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloric acid salt in Step C. ¹H NMR (500 MHz, CDCl₃) δ 8.07 (d,J=8.25 Hz, 2H), 7.61 (d, J=8.80 Hz, 2H), 7.21 (d, J=7.70 Hz, 1H), 6.01(dd, J=7.70, 2.75 Hz, 1H), 5.97 (d, J=2.75 Hz, 1H), 4.69-4.79 (m, 1H),4.38 (app brs, 1H), 4.30 (app brs, 1H), 3.09 (s, 3H), 2.00-2.26 (m, 4H),1.67-1.90 (m, 4H), 1.73 (d, J=16.50 Hz, 6H). MS (ESI) 529 (M+H).

Example 33 Preparation of (3-exo)-1,3-difluoro-2-methylpropan-2-yl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Example 33 was prepared according to procedures described in Example 2,Step B-C, substituting 1,3-difluoro-2-methylpropan-2-ol for1,1,1-trifluoro-2-propanol in Step B and(3-exo)-4-(8-azabicyclo[3.2.1]octan-3-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-onehydrochloric acid salt for1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloric acid salt in Step C. ¹H NMR (500 MHz, CDCl₃) δ 8.07 (d,J=8.80 Hz, 2H), 7.61 (d, J=8.80 Hz, 2H), 7.21 (d, J=7.70 Hz, 1H), 6.01(dd, J=7.42, 2.47 Hz, 1H), 5.97 (d, J=2.75 Hz, 1H), 4.69-4.78 (m, 2H),4.63 (dd, J=9.35, 2.20 Hz, 1H), 4.54 (dd, J=9.35, 2.20 Hz, 1H), 4.37(app brs, 1H), 4.32 (app brs, 1H), 3.09 (s, 3H), 2.03-2.23 (m, 4H),1.69-1.89 (m, 4H), 1.56 (t, J=2.20 Hz, 3H). MS (ESI) 511 (M+H).

Example 34 Preparation of (3-exo)-1,1,1-trifluoropropan-2-yl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Example 34 was prepared according to procedures described in Example 2,StepC, substituting(3-exo)-4-(8-azabicyclo[3.2.1]octan-3-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-onehydrochloric acid salt for1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloric acid salt. ¹H NMR (500 MHz, CDCl₃) δ 8.08 (d, J=8.80 Hz,2H), 7.61 (d, J=8.80 Hz, 2 H), 7.24 (d, J=7.70 Hz, 1H), 6.16 (s, 1H),6.01-6.11 (m, 1H), 5.23-5.36 (m, 1H), 4.72-4.83 (m, 1H), 4.38-4.49 (m,2H), 3.10 (s, 3H), 1.65-2.31 (m, 8H), 1.38-1.51 (m, 3H). MS (ESI) 515(M+H).

Example 35 Preparation of (3-exo)-sec-butyl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Example 35 was prepared according to procedures described in Example 2,Step B-C, substituting 2-butanol for 1,1,1-trifluoro-2-propanol in StepB and(3-exo)-4-(8-azabicyclo[3.2.1]octan-3-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-onehydrochloric acid salt for1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloric acid salt in Step C. ¹H NMR (500 MHz, CDCl₃) δ 8.08 (d,J=8.80 Hz, 2H), 7.61 (d, J=8.25 Hz, 2H), 7.25 (d, J=7.70 Hz, 1 H), 6.22(d, J=2.75 Hz, 1H), 6.09 (dd, J=7.42, 2.47 Hz, 1H), 4.72-4.84 (m, 2H),4.33-4.46 (m, 2H), 3.10 (s, 3H), 2.00-2.23 (m, 4H), 1.50-1.95 (m, 6H),1.25 (d, J=6.05 Hz, 3H), 0.94 (app brs, 3H). MS (ESI) 475 (M+H).

Example 36 Preparation of(3-exo)-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Example 36 was prepared according to procedures described in Example 2,Step B-C, substituting 1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-ol for1,1,1-trifluoro-2-propanol in Step B and(3-exo)-4-(8-azabicyclo[3.2.1]octan-3-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-onehydrochloric acid salt for1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloric acid salt in Step C. ¹H NMR (500 MHz, CDCl₃) δ 8.10 (d,J=8.25 Hz, 2H), 7.61 (d, J=8.80 Hz, 2H), 7.32 (d, J=7.70 Hz, 1H), 6.61(d, J=2.75 Hz, 1H), 6.54 (s, 1H), 6.22 (dd, J=7.70, 2.75 Hz, 1H),4.82-4.94 (m, 1H), 4.58-4.65 (m, 1H), 4.48-4.57 (m, 1H), 3.93 (s, 3H),3.12 (s, 3H), 2.07-2.35 (m, 4H), 1.84-2.00 (m, 4H). MS (ESI) 567 (M+H).

Example 37 Preparation of (3-exo)-4-methoxyphenyl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Example 37 was prepared according to procedures described in Example 2,Step C, substituting(3-exo)-4-(-8-azabicyclo[3.2.1]octan-3-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-onehydrochloric acid salt for1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloric acid salt and 4-methoxyphenyl chloroformate for1,1,1-trifluoropropan-2-yl chloroformate. ¹H NMR (500 MHz, CDCl₃) δ 8.09(d, J=8.25 Hz, 2H), 7.61 (d, J=8.80 Hz, 2H), 7.28 (d, J=7.70 Hz, 1H),7.06 (d, J=8.80 Hz, 2H), 6.89 (d, J=8.80 Hz, 2H), 6.35 (d, J=2.75 Hz,1H), 6.14 (dd, J=7.70, 2.20 Hz, 1H), 4.79-4.92 (m, 1H), 4.60 (app brs,1H), 4.51 (app brs, 1H), 3.80 (s, 3H), 3.11 (s, 3H), 2.08-2.35 (m, 4H),1.77-2.01 (m, 4H). MS (ESI) 525 (M+H).

Example 38 Preparation of tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-ylthio)piperidine-1-carboxylate

Step A. Preparation of4-bromo-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

A mixture of 4-hydroxy-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one(106.1 mg, 0.4 mmol) and phosphorous oxybromide (573.4 mg, 2.0 mmol,Alfa Aesar) was heated at 100° C. for 45 min and then cooed to roomtemperature. To the above residue was added saturated NaHCO₃ aqueoussolution at 0° C. followed by extraction with CH₂Cl₂ (3×). The combinedextracts were washed with saturated NaHCO₃ aqueous solution and brine,dried (Na₂SO₄) and evaporated. The residual was purified by flashchromatography (0 to 100% EtOAc/hexanes) to yield 60.7 mg (46%) of theproduct as a yellow solid. MS (ESI) 328 (M+H).

Step B. Example 38

To a solution of tert-butyl 4-mercaptopiperidine-1-carboxylate (65.2 mg,0.3 mmol, prepared according to procedures described in U.S. Pat. No.6,566,384 B1) in DMF (1.5 mL) at 0° C. was added sodium hydride (37 mg,1.0 mmol, 65% dispersion in mineral oil, Aldrich). After stirring at 0°C. for 30 min, 4-bromo-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one (82mg, 0.25 mmol) in DMF (1.2 mL) was added. The resulting mixture wasstirred at room temperature for 50 min and then quenched with saturatedNH₄Cl aqueous solution (0.5 mL). The reaction mixture was diluted withEtOAc and H₂O and the aqueous layer was extracted further with EtOAc(3×). The combined extracts were washed with brine/H₂O (1:1, 3×), dried(Na₂SO₄) and evaporated. The residual was purified by flashchromatography (0 to 100% EtOAc/hexanes) to yield 100.6 mg (72%) ofExample 38 as a light yellow solid. ¹H NMR (500 MHz, CDCl₃) δ ppm 8.08(d, J=8.25 Hz, 2H), 7.62 (d, J=8.25 Hz, 2H), 7.18 (d, J=7.15 Hz, 1H),6.41 (d, J=2.20 Hz, 1H), 6.14 (dd, J=7.15, 2.20 Hz, 1H), 3.98 (app brs,2H), 3.43-3.52 (m, 1H), 3.03-3.16 (m, 2H), 3.10 (s, 3H), 2.06-2.16 (m,2H), 1.61-1.73 (m, 2H), 1.47 (s, 9H). MS (ESI) 465 (M+H).

Example 39 Preparation of isopropyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-ylthio)piperidine-1-carboxylate

Example 39 was prepared according to procedures described in Example 3substituting tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-ylthio)piperidine-1-carboxylatefor tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate.¹H NMR (500 MHz, CDCl₃) δ 8.09 (d, J=8.80 Hz, 2H), 7.62 (d, J=8.80 Hz,2H), 7.22 (d, J=7.70 Hz, 1H), 6.66 (d, J=1.65 Hz, 1H), 6.27 (dd, J=7.42,1.92 Hz, 1H), 4.88-5.00 (m, 1H), 4.04 (app brs, 2H), 3.47-3.58 (m, 1H),3.12-3.17 (m, 2H), 3.11 (s, 3H), 2.08-2.16 (m, 2H), 1.61-1.73 (m, 2H),1.26 (d, J=6.05 Hz, 6H). MS (ESI) 451 (M+H).

Example 40 Preparation of tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyrimidin-4-yloxy)piperidine-1-carboxylate

Step A. Preparation of tert-butyl4-(2-chloropyrimidin-4-yloxy)piperidine-1-carboxylate

To a solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (1.0 g,5.0 mmol, Aldrich) in DMF (15.0 mL) at 0° C. was added sodium hydride(0.55 g, 15.0 mmol, 65% dispersion in mineral oil, commerciallyavailable from Sigma-Aldrich Corporation). in several portions. Afterstirring at 0° C. for 10 min, 2,4-dichloropyrimidine (745 mg, 5.0 mmol,commercially available from Sigma-Aldrich Corporation) in DMF (10.0 mL)was added. The resulting mixture was stirred at 0° C. for 10 min and atroom temperature for 2 h and then quenched with saturated NH₄Cl aqueoussolution (1.5 mL). The reaction mixture was diluted with EtOAc and H₂Oand the aqueous solution was extracted further with EtOAc (2×). Thecombined organic extracts were washed with H₂O (3×) and brine, dried(Na₂SO₄) and evaporated. The residual was purified by flashchromatography (0 to 50% EtOAc/hexanes) to yield 409.3 mg (26%) of theproduct as an off-white semi-solid. MS (ESI) 314 (M+H).

Step B. Preparation of tert-butyl4-(2-oxo-1,2-dihydropyrimidin-4-yloxy)piperidine-1-carboxylate

A mixture of tert-butyl4-(2-chloropyrimidin-4-yloxy)piperidine-1-carboxylate (341.5 mg, 0.90mmol), potassium carbonate (225.6 mg, 1.64 mmol, EMD) and1,4-diazacyclo[2,2,2]octane (48.8 mg, 0.44 mmol, commercially availablefrom Alfa Aesar) in dioxane/H₂O (10 mL/10 mL) was heated at 70° C. for 6h, cooled to room temperature and then evaporated. The residual waspurified by flash chromatography (0 to 10% MeOH/CH₂Cl₂) to yield 275 mg(85%) of the product as an off-white solid.

Step C Example 40

A mixture of tert-butyl4-(2-oxo-1,2-dihydropyrimidin-4-yloxy)piperidine-1-carboxylate (266.5mg, 0.90 mmol,), 4-bromophenyl methyl sulfone (212.2 mg, 0.90 mmol,commercially available from Sigma-Aldrich Corporation), copper(I) iodide(60.4 mg, 0.32 mmol, commercially available from Sigma-AldrichCorporation), 8-hydroxyquinoline (47 mg, 0.32 mmol, commerciallyavailable from Alfa Aesar) and potassium carbonate (188 mg, 1.35 mmol,EMD) in DMSO (7.5 mL) was heated under Microwave conditions (160° C., 30min) and cooled to room temperature. The reaction mixture was dilutedwith EtOAc and then filtered. The filtrate was washed with H₂O and theaqueous layer was back extracted with EtOAc (2×). The combined organiclayers were washed with H₂O/brine (1:1, 4×), dried (Na₂SO₄) andevaporated. The residual was purified by flash chromatography (0 to 100%EtOAc/Hexanes, twice) to yield 168.5 mg (55%) of Example 40 as a yellowsolid. ¹H NMR (500 MHz, CDCl₃) δ 8.08 (d, J=8.25 Hz, 2 H), 7.63 (d,J=8.25 Hz, 2H), 7.54 (d, J=7.15 Hz, 1H), 6.05 (d, J=7.70 Hz, 1H),5.44-5.57 (m, 1H), 3.80 (app brs, 2H), 3.18-3.31 (m, 2H), 3.10 (s, 3H),1.95-2.08 (m, 2H), 1.65-1.85 (m, 2H), 1.48 (s, 9H). MS (ESI) 450 (M+H).

Example 41 Preparation of prop-1-en-2-yl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 41 was prepared according to procedures described in Example 2,Step C, substituting isopropenyl chloroformate for1,1,1-trifluoropropan-2-yl chloroformate. ¹H NMR (500 MHz, CDCl₃) δ 8.07(d, J=8.80 Hz, 2H), 7.62 (d, J=8.25 Hz, 2H), 7.24 (d, J=7.15 Hz, 1H),6.06 (dd, J=7.70, 2.75 Hz, 1H), 5.98 (d, J=2.75 Hz, 1H), 4.69 (d, J=5.50Hz, 2H), 4.50-4.59 (m, 1H), 3.72-3.83 (m, 2H), 3.43-3.53 (m, 2H), 3.09(s, 3H), 1.99-2.08 (m, 2H), 1.97 (s, 3H), 1.86 (app brs, 2 H). MS (ESI)433 (M+H).

Example 42 Preparation ofN-tert-butyl-4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxamide

To a suspension of1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloric acid salt (20 mg, 0.052 mmol) in CH₂Cl₂ (1.0 mL) was addedEt₃N (36.2 μL, 0.26 mmol) followed by addition of tert-butyl isocyanate(14.8 μL, 0.13 mmol, commercially available from Sigma-AldrichCorporation). The reaction mixture was stirred for 1.5 h and evaporatedunder reduced pressure. The crude product was purified by preparativeHPLC (C₁₈ column; 0-100% methanol in water containing 0.05%trifluoroacetic acid) to give 15.4 mg (62%) of Example 42 as anoff-white solid. ¹H NMR (500 MHz, CDCl₃) δ 8.10 (d, J=8.80 Hz, 2H), 7.61(d, J=8.25 Hz, 2H), 7.36 (d, J=7.70 Hz, 1H), 6.51 (d, J=2.75 Hz, 1H),6.30 (dd, J=7.42, 2.47 Hz, 1H), 4.54-4.68 (m, 1H), 3.55-3.70 (m, 2H),3.26-3.39 (m, 2H), 3.12 (s, 3H), 2.01-2.13 (m, 2H), 1.80-1.95 (m, 2H),1.37 (s, 9H). MS (ESI) 448 (M+H).

Example 43 Preparation of 4-chlorophenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 43 was prepared according to procedures described in Example 2substituting 4-chlorophenyl chloroformate for 1,1,1-trifluoropropan-2-ylchloroformate at Step C. ¹H NMR (400 MHz, CDCl₃) δ 8.01 (d, J=8.3 Hz,2H), 7.55 (d, J=8.3 Hz, 2H), 7.25 (d, J=7.5 Hz, 2H), 7.20 (d, J=7.5 Hz,1H), 7.00 (d, J=7.5 Hz, 2H), 6.07-6.09 (m, 2H), 4.55 (app brs, 1H),3.70-3.89 (m, 2H), 3.47-3.63 (m, 2H), 3.04 (s, 3H), 1.94-2.09 (m, 2H),1.89-1.91 (m, 2H). MS (ESI) 503 (M+H).

Example 44 Preparation of 4-fluorophenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 44 was prepared according to procedures described in Example 2substituting 4-fluorophenyl chloroformate for 1,1,1-trifluoropropan-2-ylchloroformate at Step C. ¹H NMR (400 MHz, CDCl₃) δ 8.02 (d, J=7.5 Hz,2H), 7.55 (d, J=7.5 Hz, 2H), 7.20 (d, J=7.5 Hz, 1H), 7.09 (d, J=8.5 Hz,2H), 6.93 (d, J=8.5 Hz, 2H), 6.15-6.20 (m, 2H), 4.57 (app brs, 1H),3.70-3.89 (m, 2H), 3.45-3.63 (m, 2H), 3.05 (s, 3H), 1.92-2.06 (m, 2H),1.79-1.89 (m, 2H). MS (ESI) 487 (M+H).

Example 45 Preparation of 4-methylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 45 was prepared according to procedures described in Example 2substituting 4-methylphenyl chloroformate for 1,1,1-trifluoropropan-2-ylchloroformate at Step C. ¹H NMR (400 MHz, CDCl₃) δ 8.02 (d, J=7.5 Hz,2H), 7.56 (d, J=7.5 Hz, 2H), 7.20 (d, J=7.5 Hz, 1H), 6.98-7.02 (m, 4H),6.15-6.20 (m, 2H), 4.57 (app brs, 1H), 3.70-3.89 (m, 2H), 3.45-3.63 (m,2H), 3.05 (s, 3H), 2.27 (s, 3H), 1.92-2.06 (m, 2H), 1.79-1.89 (m, 2H).MS (ESI) 483 (M+H).

Example 46 Preparation of 4-methoxyphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 46 was prepared according to procedures described in Example 2substituting 4-methoxyphenyl chloroformate for1,1,1-trifluoropropan-2-yl chloroformate at Step C. ¹H NMR (400 MHz,CDCl₃) δ 8.02 (d, J=7.5 Hz, 2H), 7.55 (d, J=7.5 Hz, 2H), 7.20 (d, J=7.5Hz, 1H), 6.95 (d, J=8.5 Hz, 2H), 6.81 (d, J=8.5 Hz, 2H), 6.07-6.10 (m,2H), 4.55 (app brs, 1H), 3.74-3.89 (m, 2H), 3.73 (s, 3H), 3.44-3.59 (m,2H), 3.03 (s, 3H), 1.92-2.06 (m, 2H), 1.79-1.89 (m, 2H). MS (ESI) 499(M+H).

Example 47 Preparation of 3-trifluoromethylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 47 was prepared according to procedures described in Example 2substituting 3-trifluoromethylphenyl chloroformate for1,1,1-trifluoropropan-2-yl chloroformate at Step C. ¹H NMR (400 MHz,CDCl₃) δ 8.02 (d, J=7.5 Hz, 2H), 7.55 (d, J=7.5 Hz, 2H), 7.40-7.47 (m,2H) 7.34 (s, 1H) 7.25-7.30 (m, 1H), 7.22 (d, J=7.5 Hz, 1H), 6.07-6.10(m, 2H), 4.57 (app brs, 1H), 3.70-3.89 (m, 2H), 3.47-3.64 (m, 2H), 3.03(s, 3H), 1.92-2.06 (m, 2H), 1.79-1.89 (m, 2H). MS (ESI) 537 (M+H).

Example 48 Preparation of 2-chlorophenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 48 was prepared according to procedures described in Example 2substituting 2-chlorophenyl chloroformate for 1,1,1-trifluoropropan-2-ylchloroformate at Step C. ¹H NMR (400 MHz, CDCl₃) δ 8.02 (d, J=7.5 Hz,2H), 7.55 (d, J=7.5 Hz, 2H), 7.37 (d, J=7.5 Hz, 1H), 7.06-7.22 (m, 4H),6.07-6.09 (m, 2H), 4.56 (app brs, 1H), 3.89-3.95 (m, 1H), 3.72-3.82 (m,1H), 3.61-3.69 (m, 1H), 3.45-3.55 (m, 1H), 3.03 (s, 3H), 1.92-2.06 (m,2H), 1.79-1.89 (m, 2H). MS (ESI) 503 (M+H).

Example 49 Preparation of (±)-4-chlorophenyl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)pyrrolidine-1-carboxylate

Example 49 was prepared according to procedures described in Examples 1and 2 substituting tert-butyl3-(methylsulfonyloxy)pyrrolidine-1-carboxylate for tert-butyl4-(methylsulfonyloxy)piperidine-1-carboxylate in Example 1 at Step C,and 4-chlorophenyl chloroformate for 1,1,1-trifluoropropan-2-ylchloroformate in Example 2 at Step C. ¹H NMR (400 MHz, CDCl₃) δ 8.01 (d,J=8.3 Hz, 2H), 7.55 (d, J=8.3 Hz, 2H), 7.26 (d, J=7.5 Hz, 2H), 7.20 (d,J=7.5 Hz, 1H), 7.04 (d, J=7.5 Hz, 2H), 6.00-6.05 (m, 1H), 5.95 (s, 1H)4.92 (app brs, 1H), 3.70-3.89 (m, 2 H), 3.53-3.86 (m, 2H), 3.04 (s, 3H),2.13-2.35 (m, 2H). MS (ESI) 489 (M+H).

Example 50 Preparation of (±)-benzyl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)pyrrolidine-1-carboxylate

Example 50 was prepared according to procedures described in Example 49substituting benzyl chloroformate for 4-chlorophenyl chloroformate. ¹HNMR (400 MHz, CDCl₃) δ 8.00 (d, J=8.3 Hz, 2H), 7.53 (d, J=8.3 Hz, 2H),7.22-7.35 (m, 5H), 7.18 (d, J=7.5 Hz, 1H), 5.98 (d, J=7.8 Hz, 2H), 5.88(d, J=7.8 Hz, 2 H), 5.09 (s, 2H) 4.84 (app brs, 1H), 3.45-3.79 (m, 4H),3.02 (s, 3H), 2.06-2.25 (m, 2H). MS (ESI) 469 (M+H).

Example 51 Preparation of4-(1-(benzo[d]oxazol-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 51 was prepared according to procedures described in Example 2substituting 2-chlorobenzoxazole for 1,1,1-trifluoropropan-2-ylchloroformate at Step C and the reaction was heated at 100° C. for 10min. ¹H NMR (400 MHz, CDCl₃) δ 8.00 (d, J=7.5 Hz, 2H), 7.55 (d, J=7.5Hz, 2H), 7.35 (d, J=7.5 Hz, 1H), 7.20 (app t, J=8.5 Hz, 2H), 7.14 (t,J=8.5 Hz, 1H), 7.01 (t, J=8.5 Hz, 1H), 6.01 (d, J=7.5 Hz, 1H), 5.94 (s,1H), 4.56 (app brs, 1H), 3.87-3.95 (m, 2H), 3.68-3.75 (m, 2 H), 3.02 (s,3H), 2.03-2.12 (m, 2H), 1.89-1.97 (m, 2H). MS (ESI) 466 (M+H).

Example 52 Preparation of4-(1-(5-methylbenzo[d]oxazol-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 52 was prepared according to procedures described in Example 51substituting 2-chloro-5-methyl-benzoxazole for 2-chlorobenzoxazole. ¹HNMR (400 MHz, CDCl₃) δ 8.07 (d, J=7.5 Hz, 2H), 7.61 (d, J=7.5 Hz, 2H),7.22-7.26 (m, 2H), 7.15 (d, J=8.5 Hz, 1H), 6.88 (d, J=8.0 Hz, 1H), 6.08(d, J=7.5 Hz, 1 H), 5.99 (s, 1H), 4.62 (app brs, 1H), 3.91-3.98 (m, 2H),3.68-3.85 (m, 2H), 3.09 (s, 3H), 2.10-2.28 (m, 2H), 1.98-2.07 (m, 2H).MS (ESI) 480 (M+H).

Example 53 Preparation of cyclopropyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 53 was prepared according to procedures described in Example 2substituting cyclopropyl chloroformate for 1,1,1-trifluoropropan-2-ylchloroformate at Step C. ¹H NMR (400 MHz, CDCl₃) δ 8.05 (d, J=8.5 Hz,2H), 7.60 (d, J=8.5 Hz, 2H), 7.23 (d, J=7.5 Hz, 1H), 6.04 (d, J=7.5 Hz,1H), 5.98 (s, 1H), 5.09-5.13 (m, 1H), 4.47-4.50 (m, 1H), 3.69-3.76 (m,2H), 3.34-3.40 (m, 2H), 3.08 (s, 3H), 1.55-2.06 (m, 12H). MS (ESI) 461(M+H).

Example 54 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(pyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 54 was prepared according to procedures described in Example 51substituting 2-chloropyrimidine for 2-chlorobenzoxazole. ¹H NMR (400MHz, CDCl₃) δ 8.29 (d, J=4.8 Hz, 2H), 8.00 (d, J=8.5 Hz, 2H), 7.55 (d,J=8.5 Hz, 2 H), 7.17 (d, J=7.5 Hz, 1H), 6.49 (d, J=4.8 Hz, 1H), 6.00 (d,J=7.5 Hz, 1H), 5.95 (s, 1H), 4.52-4.55 (m, 1H), 4.10-4.19 (m, 2H),3.65-3.76 (m, 2H), 3.03 (s, 3 H), 1.98-2.06 (m, 2H), 1.77-1.89 (m, 2H).MS (ESI) 427 (M+H).

Example 55 Preparation of4-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 55 was prepared according to procedures described in Example 51substituting 2-chloro-5-ethylpyrimidine for 2-chlorobenzoxazole. ¹H NMR(400 MHz, CDCl₃) δ 8.27 (s, 2H), 8.05 (d, J=8.5 Hz, 2H), 7.61 (d, J=8.5Hz, 2H), 7.23 (d, J=7.5 Hz, 1H), 6.09 (d, J=7.5 Hz, 1H), 5.99 (s, 1H),4.60-4.64 (m, 1H), 4.10-4.19 (m, 2H), 3.85-4.02 (m, 2H), 3.08 (s, 3H),2.51 (q, J=7.1 Hz, 2H), 2.03-2.14 (m, 2H), 1.89-1.98 (m, 2H), 1.23 (t,J=7.1 Hz, 3H). MS (ESI) 455 (M+H).

Example 56 Preparation of4-(1-(5-fluoropyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 56 was prepared according to procedures described in Example 51substituting 2-chloro-5-fluoropyrimidine for 2-chlorobenzoxazole. ¹H NMR(400 MHz, CDCl₃) δ 8.23 (s, 2H), 8.05 (d, J=8.5 Hz, 2H), 7.60 (d, J=8.5Hz, 2H), 7.23 (d, J=7.5 Hz, 1H), 6.08 (d, J=7.5 Hz, 1H), 6.01 (s, 1H),4.56-4.61 (m, 1H), 4.10-4.19 (m, 2H), 3.69-4.76 (m, 2H), 3.08 (s, 3H),2.03-2.11 (m, 2H), 1.80-1.92 (m, 2H). MS (ESI) 445 (M+H).

Example 57 Preparation of4-(1-(5-bromopyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 57 was prepared according to procedures described in Example 51substituting 2-chloro-5-bromopyrimidine for 2-chlorobenzoxazole. ¹H NMR(400 MHz, CDCl₃) δ 8.33 (s, 2H), 8.07 (d, J=8.5 Hz, 2H), 7.62 (d, J=8.5Hz, 2H), 7.24 (d, J=7.5 Hz, 1H), 6.08 (d, J=7.5 Hz, 1H), 6.03 (s, 1H),4.58-4.64 (m, 1H), 4.08-4.15 (m, 2H), 3.72-4.82 (m, 2H), 3.09 (s, 3H),1.99-2.12 (m, 2H), 1.82-1.94 (m, 2H). MS (ESI) 505 (M+H).

Example 58 Preparation of4-(1-(4-methylpyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 58 was prepared according to procedures described in Example 51substituting 2-chloro-4-methylpyrimidine for 2-chlorobenzoxazole. ¹H NMR(400 MHz, CDCl₃) δ 8.16 (d, J=6.1 Hz, 1H), 8.10 (d, J=8.5 Hz, 2H), 7.55(d, J=8.5 Hz, 2H), 7.19 (d, J=7.5 Hz, 1H), 6.45 (d, J=6.1 Hz, 1H), 6.00(d, J=7.5 Hz, 1 H), 5.94 (s, 1H), 4.55-4.60 (m, 1H), 4.11-4.18 (m, 2H),3.87-4.96 (m, 2H), 3.03 (s, 3H), 2.39 (s, 3H), 2.01-2.12 (m, 2H),1.82-1.94 (m, 2H). MS (ESI) 441 (M+H).

Example 59 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(pyridin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 59 was prepared according to procedures described in Example 51substituting 2-chloro-pyridine for 2-chlorobenzoxazole. ¹H NMR (400 MHz,CDCl₃) δ 8.10 (d, J=8.5 Hz, 2H), 8.09 (d, J=8.1 Hz, 1H), 7.68 (d, J=8.5Hz, 2H), 7.55-7.61 (m, 2H), 6.92 (d, J=8.1 Hz, 1H), 6.87 (t, J=8.1 Hz,1H), 6.26 (d, J=7.5 Hz, 1H), 6.09 (s, 1H), 4.83-4.89 (m, 1H), 3.88-3.96(m, 2H), 3.43-3.51 (m, 2H), 3.07 (s, 3H), 2.09-2.17 (m, 2H), 1.80-1.90(m, 2H). MS (ESI) 426 (M+H).

Examples 60 and 61 Preparation of trans-ethyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)cyclohexanecarboxylateand cis-ethyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)cyclohexanecarboxylate

Examples 60 and 61 were prepared according to procedures described inExample 1 substituting a mixture of cis and trans ethyl4-hydroxycyclohexane-carboxylate fort-tert-butyl-4-hydroxy-1-piperidinecarboxylate to yield separatedproducts by flash chromatography (0 to 100% EtOAc in hexanes). Example60: ¹H NMR (400 MHz, CDCl₃) δ 8.06 (d, J=8.5 Hz, 2H), 7.60 (d, J=8.5 Hz,2H), 7.23 (d, J=7.5 Hz, 1H), 6.09 (s, 1H), 6.06 (d, J=7.5 Hz, 1H),4.24-4.31 (m, 1H), 4.13 (q, J=7.2 Hz, 2H), 3.08 (s, 3H), 2.31-2.46 (m,2H), 2.10-2.25 (m, 2H), 1.47-1.70 (m, 5H), 1.26 (t, J=7.2 Hz, 3H). MS(ESI) 420 (M+H); and Example 61: ¹H NMR (400 MHz, CDCl₃) δ 8.06 (d,J=8.5 Hz, 2H), 7.60 (d, J=8.5 Hz, 2H), 7.29 (d, J=7.5 Hz, 1H), 6.35 (s,1H), 6.21 (d, J=7.5 Hz, 1H), 4.54-4.61 (m, 1H), 4.13 (q, J=7.2 Hz, 2H),3.08 (s, 3H), 2.31-2.46 (m, 2H), 2.10-2.25 (m, 2H), 1.47-1.70 (m, 5H),1.25 (t, J=7.2 Hz, 3H). MS (ESI) 420 (M+H).

Example 62 Preparation of4-((trans)-4-(3-isopropyl-1,2,4-oxadiazol-5-yl)cyclohexyloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Step A. Preparation oftrans-4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)cyclohexanecarboxylate

To a stirring solution of trans-ethyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)cyclohexanecarboxylate(500 mg, 1.19 mmol) in MeOH (10 mL), water (1 mL), and DMF (1 mL) atroom temperature was added sodium hydroxide (120 mg, 3.0 mmol,commercially available from EM Science). The reaction mixture wasstirred overnight and then concentrated in vacuo to dryness. The residuewas portioned between EtOAc and water. The reaction was then acidifiedto pH 2 with concentrated HCl and stirred for 20 min. The solid wasfiltered and washed with EtOAc. The solid was dried in vacuo at to yield454 mg of desired product as a white solid. MS (ESI) 392 (M+H).

Step B Example 62

To a stirring solution oftrans-4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)cyclohexanecarboxylate(100 mg, 0.26 mmol) in dry DMF (2 mL) at room temperature was addedcarbonyl diimidazole (41 mg, 0.26 mmol, commercially available fromSigma-Aldrich Corporation). The reaction was heated to 100° C. for 30min and the isopropyl oxime (27 mg, 0.26 mmol) was added. The reactionwas stirred overnight and then quenched with brine. The reaction wasextracted with EtOAc. The organic layers were combined, dried overNa₂SO₄, and concentrated in vacuo to a pale yellow oil. The oil waspurified by flash chromatography (0 to 100% EtOAc in hexanes) to yield52 mg of Example 62 as a white solid. ¹H NMR (400 MHz, CDCl₃) δ 8.06 (d,J=8.5 Hz, 2H), 7.60 (d, J=8.5 Hz, 2H), 7.25 (d, J=7.5 Hz, 1H), 6.26 (s,1H), 6.15 (d, J=7.5 Hz, 1H), 4.31-4.42 (m, 1H), 3.09 (s, 3H), 2.96-3.08(m, 2H), 2.21-2.45 (m, 5H), 1.76-1.88 (m, 3H), 1.61-1.73 (m, 2H), 1.31(d, J=6.9 Hz, 6H). MS (ESI) 458 (M+H).

Example 63 Preparation of4-((cis)-4-(3-isopropyl-1,2,4-oxadiazol-5-yl)cyclohexyloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 63 was prepared according to procedures described in Example 62substituting cis-ethyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)cyclohexanecarboxylatefor of trans-ethyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)cyclohexanecarboxylate.¹H NMR (400 MHz, CDCl₃) δ 8.04 (d, J=8.5 Hz, 2H), 7.59 (d, J=8.5 Hz,2H), 7.20 (d, J=7.5 Hz, 1H), 6.05 (d, J=7.5 Hz, 1H), 5.94 (s, 1H),4.52-4.58 (m, 1H), 3.09 (s, 3H), 2.99-3.08 (m, 2H), 1.95-2.19 (m, 6H),1.73-1.85 (m, 2H), 1.32 (d, J=7.0 Hz, 6H). MS (ESI) 458 (M+H).

Example 64 Preparation of trans-isopropyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)cyclohexanecarboxylate

To a stirring solution oftrans-4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)cyclohexanecarboxylate(100 mg, 0.26 mmol) and diiopropylethylamine (65 mg, 0.5 mmol,commercially available from Sigma-Aldrich Corporation) in dry DMF (2 mL)at room temperature was added isopropyl iodide (85 mg, 0.5 mmol,commercially available from Sigma-Aldrich Corporation). The reaction washeated to 100° C. overnight. The reaction was cooled to room temperatureand then concentrated in vacuo to a brown solid. The solid was purifiedby flash chromatography (30 to 100% EtOAc in hexanes) to yield 65 mg ofExample 64 as a white solid. ¹H NMR (400 MHz, CDCl₃) δ 8.06 (d, J=8.5Hz, 2H), 7.60 (d, J=8.5 Hz, 2H), 7.24 (d, J=7.5 Hz, 1H), 6.08 (s, 1H),6.06 (d, J=7.5 Hz, 1H), 5.01 (sept, J=6.0 Hz, 1H), 4.24-4.28 (m, 1H),3.09 (s, 3H), 2.28-2.35 (m, 1H), 2.18-2.25 (m, 2H), 2.06-2.11 (m, 2H),1.47-1.73 (m, 4H), 1.23 (d, J=6.0 Hz, 6H). MS (ESI) 434 (M+H).

Example 65 Preparation of cis-isopropyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)cyclohexanecarboxylate

Example 65 was prepared according to procedures described in Example 66substituting cis-ethyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)cyclohexanecarboxylatefor trans-ethyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)cyclohexanecarboxylate.¹H NMR (400 MHz, CDCl₃) δ 8.03 (d, J=8.5 Hz, 2H), 7.59 (d, J=8.5 Hz,2H), 7.20 (d, J=7.5 Hz, 1H), 6.05 (d, J=7.5 Hz, 1H), 5.96 (s, 1H), 5.00(sept, J=6.2 Hz, 1H), 4.44-4.48 (m, 1H), 3.08 (s, 3H), 2.36-2.41 (m,1H), 1.99-2.08 (m, 2H), 1.83-1.95 (m, 2 H), 1.63-1.79 (m, 4H), 1.21 (d,J=6.2 Hz, 6H). MS (ESI) 434 (M+H).

Example 66 Preparation of phenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 66 was prepared according to procedures described in Example 3substituting phenyl chloroformate for isopropyl chloroformate. MS (ESI)469 (M+H).

Example 67 Preparation of4-(1-benzoylpiperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 67 was prepared according to procedures described in Example 3substituting benzoyl chloride for isopropyl chloroformate. MS (ESI) 453(M+H).

Example 68 Preparation of4-(1-(2-chlorobenzoyl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 68 was prepared according to procedures described in Example 3substituting 2-chlorobenzoyl chloride for isopropyl chloroformate. MS(ESI) 488 (M+H).

Example 69 Preparation of4-(1-(3-chlorobenzoyl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 69 was prepared according to procedures described in Example 3substituting 3-chlorobenzoyl chloride for isopropyl chloroformate. MS(ESI) 488 (M+H).

Example 70 Preparation of4-(1-(4-chlorobenzoyl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 70 was prepared according to procedures described in Example 3substituting 4-chlorobenzoyl chloride for isopropyl chloroformate. MS(ESI) 488 (M+H).

Example 71 Preparation of4-(1-(4-methoxybenzoyl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 71 was prepared according to procedures described in Example 3substituting 4-methoxybenzoyl chloride for isopropyl chloroformate. MS(ESI) 483 (M+H).

Example 72 Preparation of4-(1-(3,3-dimethylbutanoyl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 72 was prepared according to procedures described in Example 3substituting 3,3-dimethylbutanoyl chloride for isopropyl chloroformate.MS (ESI) 447 (M+H).

Example 73 Preparation of4-(1-(3-methylbutanoyl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 73 was prepared according to procedures described in Example 3substituting 3-methylbutanoyl chloride for isopropyl chloroformate. MS(ESI) 433 (M+H).

Example 74 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(3-phenylpropanoyl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 74 was prepared according to procedures described in Example 3substituting 3-phenylpropanoyl chloride for isopropyl chloroformate. MS(ESI) 481 (M+H).

Example 75 Preparation of4-(1-(cyclobutanecarbonyl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 75 was prepared according to procedures described in Example 3substituting cyclobutanecarbonyl chloride for isopropyl chloroformate.MS (ESI) 431 (M+H).

Example 76 Preparation of4-(1-(cyclopentanecarbonyl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 76 was prepared according to procedures described in Example 3substituting cyclopentanecarbonyl chloride for isopropyl chloroformate.MS (ESI) 445 (M+H).

Example 77 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(thiophene-2-carbonyl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 77 was prepared according to procedures described in Example 3substituting thiophene-2-carbonyl chloride for isopropyl chloroformate.MS (ESI) 459 (M+H).

Example 78 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(quinoxaline-2-carbonyl)piperidin-4-yloxy)pyridin-2(1H)-one,TFA salt

Example 78 was prepared according to procedures described in Example 3substituting quinoxaline-2-carbonyl chloride for isopropylchloroformate. MS (ESI) 505 (M+H).

Example 79 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(quinolin-8-ylsulfonyl)piperidin-4-yloxy)pyridin-2(1H)-one,TFA salt

Example 79 was prepared according to procedures described in Example 3substituting quinolin-8-ylsulfonyl chloride for isopropyl chloroformate.MS (ESI) 540 (M+H).

Example 80 Preparation of4-(1-(benzylsulfonyl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 80 was prepared according to procedures described in Example 3substituting benzylsulfonyl chloride for isopropyl chloroformate. MS(ESI) 503 (M+H).

Example 81 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(propylsulfonyl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 81 was prepared according to procedures described in Example 3substituting propylsulfonyl chloride for isopropyl chloroformate. MS(ESI) 455 (M+H).

Example 82 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(2,2,2-trifluoroethylsulfonyl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 82 was prepared according to procedures described in Example 3substituting 2,2,2-trifluoroethylsulfonyl chloride for isopropylchloroformate. MS (ESI) 495 (M+H).

Example 83 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(methylsulfonyl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 83 was prepared according to procedures described in Example 3substituting methylsulfonyl chloride for isopropyl chloroformate. MS(ESI) 427 (M+H).

Example 84 Preparation of4-(1-(cyclopropylsulfonyl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 84 was prepared according to procedures described in Example 3substituting cyclopropylsulfonyl chloride for isopropyl chloroformate.MS (ESI) 453 (M+H).

Example 85 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(4-phenoxyphenylsulfonyl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 85 was prepared according to procedures described in Example 3substituting phenoxyphenylsulfonyl chloride for isopropyl chloroformate.MS (ESI) 581 (M+H).

Example 86 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(pyridin-2-ylsulfonyl)piperidin-4-yloxy)pyridin-2(1H)-one,TFA salt

Example 86 was prepared according to procedures described in Example 3substituting pyridin-2-ylsulfonyl chloride for isopropyl chloroformate.MS (ESI) 490 (M+H).

Example 87 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(thiophen-3-ylsulfonyl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 87 was prepared according to procedures described in Example 3substituting thiophen-3-ylsulfonyl chloride for isopropyl chloroformate.MS (ESI) 495 (M+H).

Example 88 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-picolinoylpiperidin-4-yloxy)pyridin-2(1H)-one

Example 88 was prepared according to procedures described in Example 3substituting picolinoyl chloride for isopropyl chloroformate. MS (ESI)454 (M+H).

Example 89 Preparation of 2-methoxyethyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 89 was prepared according to procedures described in Example 3substituting 2-methoxyethyl chloroformate for isopropyl chloroformate.MS (ESI) 451 (M+H).

Example 90 Preparation of methyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 90 was prepared according to procedures described in Example 3substituting methyl chloroformate for isopropyl chloroformate. MS (ESI)407 (M+H).

Example 91 Preparation of propyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 91 was prepared according to procedures described in Example 3substituting propyl chloroformate for isopropyl chloroformate. MS (ESI)435 (M+H).

Example 92 Preparation of prop-2-ynyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 92 was prepared according to procedures described in Example 3substituting prop-2-ynyl chloroformate for isopropyl chloroformate. MS(ESI) 431 (M+H).

Example 93 Preparation of 2,2-dimethylpropyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 93 was prepared according to procedures described in Example 3substituting 2,2-dimethylpropyl chloroformate for isopropylchloroformate. MS (ESI) 463 (M+H).

Example 94 Preparation of N-isopropyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxamide

Example 94 was prepared according to procedures described in Example 3substituting isopropyl isocyanate for isopropyl chloroformate. MS (ESI)434 (M+H).

Example 95 Preparation of N-methyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxamide

Example 95 was prepared according to procedures described in Example 3substituting methyl isocyanate for isopropyl chloroformate. MS (ESI) 406(M+H).

Example 96 Preparation of N-ethyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxamide

Example 96 was prepared according to procedures described in Example 3substituting ethyl isocyanate for isopropyl chloroformate. MS (ESI) 420(M+H).

Example 97 Preparation of N-propyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxamide

Example 97 was prepared according to procedures described in Example 3substituting propyl isocyanate for isopropyl chloroformate. MS (ESI) 434(M+H).

Example 98 Preparation of N-cyclohexyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxamide

Example 98 was prepared according to procedures described in Example 3substituting cyclohexyl isocyanate for isopropyl chloroformate. MS (ESI)474 (M+H).

Example 99 Preparation of N-benzyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxamide

Example 99 was prepared according to procedures described in Example 3substituting benzyl isocyanate for isopropyl chloroformate. MS (ESI) 481(M+H).

Example 100 Preparation of N-4-methoxybenzyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxamide

Example 100 was prepared according to procedures described in Example 3substituting 4-methoxybenzyl isocyanate for isopropyl chloroformate. MS(ESI) 512 (M+H).

Example 101 Preparation of N-cyclopentyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxamide

Example 101 was prepared according to procedures described in Example 3substituting cyclopentyl isocyanate for isopropyl chloroformate. MS(ESI) 460 (M+H).

Example 102 Preparation of N-cyclohexylmethyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxamide

Example 102 was prepared according to procedures described in Example 3with substitution of cyclohexylmethyl isocyanate for isopropylchloroformate. MS (ESI) 488 (M+H).

Example 103 Preparation of 4-tert-butylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 103 was prepared according to procedures described in Example 2substituting 4-tert-butylphenol for 1,1,1-trifluoro-2-propanol at StepB. ¹H NMR (500 MHz, CDCl₃) δ 8.08 (d, J=8.80 Hz, 2H), 7.63 (d, J=8.80Hz, 2H), 7.38 (d, J=8.80 Hz, 2H), 7.19-7.30 (m, 1H), 7.03 (d, J=8.80 Hz,2H), 6.09 (dd, J=7.70, 2.75 Hz, 1H), 6.02 (d, J=2.75 Hz, 1H), 4.52-4.66(m, 1H), 3.90 (app brs, 1H), 3.77-3.89 (m, 1H), 3.59-3.72 (m, 1H), 3.56(app brs, 1H), 3.10 (s, 9H), 2.08 (m, 2H), 1.83-1.99 (m, 2H), 1.32 (s,9H). MS (ESI) 525 (M+H).

Example 104 Preparation of 4-isopropylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 104 was prepared according to procedures described in Example 2substituting 4-isopropylphenol for 1,1,1-trifluoro-2-propanol at step B.¹H NMR (500 MHz, CDCl₃) δ 8.09 (d, J=8.25 Hz, 2H), 7.62 (d, J=8.80 Hz,2H), 7.29 (d, J=7.70 Hz, 1H), 7.22 (d, J=8.80 Hz, 2H), 7.02 (d, J=8.25Hz, 2H), 6.13-6.21 (m, 2 H), 4.57-4.66 (m, 1H), 3.91 (app brs, 1H),3.79-3.89 (m, 1H), 3.59-3.69 (m, 1 H), 3.55 (app brs, 1H), 3.10 (s, 3H),2.85-2.96 (m, 1H), 2.09 (app brs, 2H), 1.84-2.00 (m, 2H), 0.24 (d,J=6.60 Hz, 6H). MS (ESI) 511 (M+H).

Example 105 Preparation of4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

A mixture of4-(1-(5-bromopyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one(47.0 mg, 0.093 mmol), potassium carbonate (64 mg, 0.47 mmol, EMD) andcyclopropylboronic acid (24 mg, 0.28 mmol, Aldrich) in THF (0.8 mL) andWater (0.1 mL) was degassed by vacuum and purged with Argon. To theresulting mixture was added1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (7.65 mg, 9.30 μmol, Aldrich) and then stirredunder Argon at 66° C. for 3 h. The reaction mixture was cooled to roomtemperature followed by addition of another portion ofcyclopropylboronic acid (24 mg, 0.28 mmol, Aldrich) and1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (7.65 mg, 9.30 μmol, Aldrich). Reaction mixturewas stirred under Argon at 66° C. for another 3 hours and thenconcentrated in vacuo to a brown solid. The solid was purified by flashchromatography (SiO₂, 0 to 100% EtOAc in hexanes) to yield 18 mg ofExample 105 as an off-white solid. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.13(s, 2 H) 8.07 (d, J=8.31 Hz, 2H), 7.62 (d, J=8.31 Hz, 2H), 7.23 (d,J=7.83 Hz, 1H), 6.06 (d, J=7.82 Hz, 1H), 6.00 (s, 1H), 4.55-4.59 (m,1H), 4.15-4.21 (m, 2H), 3.59-3.66 (m, 2H), 3.09 (s, 3H), 2.03-2.10 (m,2H), 1.79-1.88 (m, 2H), 1.68-1.75 (m, 1H), 0.88-0.94 (m, 2H), 0.56-0.62(m, 2H). MS (ESI) 467 (M+H).

Example 106 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one,TFA salt

Step A. Preparation of1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloric acid salt

A mixture of tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(5.279 g, 11.77 mmol) and hydrogen chloride (37% in H₂O, 40 mL, EMD) wasstirred for 20 min and then concentrated in vacuo. The obtained solidwas dissolved in methanol (80 mL) and diethyl ether (300 mL) was added.The resulting solid was filtered to give 4.52 g of the desired productas an off-white solid. MS (ESI) 349 (M+H).

Step B Example 106

To a stirring suspension of1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloric acid salt (4.50 g, 11.7 mmol) and potassium carbonate (6.46g, 46.8 mmol, EMD) in dry DMF (180 mL) at room temperature was added2-chloro-5-propylpyrimidine (2.75 g, 17.54 mmol, WAKO). The reactionmixture was heated to 100° C. for 12 hours and then concentrated invacuo to a brown solid. The solid was purified by flash chromatography(SiO₂, 0 to 15% MeOH in CH₂Cl₂ and SiO₂, 0 to 100% EtOAc in CH₂Cl₂) toyield 3.988 g of Example 106 as a light yellow solid. ¹H NMR (400 MHz,CDCl₃) δ ppm 8.17 (s, 2H), 8.07 (d, J=8.31 Hz, 2H), 7.62 (d, J=8.80 Hz,2H), 7.23 (d, J=7.83 Hz, 1H), 6.07 (dd, J=7.83, 2.45 Hz, 1H), 6.02 (d,J=2.45 Hz, 1H), 4.54-4.61 (m, 1H), 4.15-4.23 (m, 2H), 3.59-3.69 (m, 2H),3.09 (s, 3H), 2.41 (t, J=7.58 Hz, 2H), 2.04-2.12 (m, 2H), 1.79-1.90 (m,2H), 1.53-1.62 (m, 2H), 0.94 (t, J=7.34 Hz, 3H). MS (ESI) 469 (M+H).

Example 107 Preparation of 4-propylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 107 was prepared according to procedures described in Example 2substituting 4-propylphenol for 1,1,1-trifluoro-2-propanol at Step B. ¹HNMR (500 MHz, CDCl₃) δ 8.08 (d, J=8.80 Hz, 2H), 7.62 (d, J=8.25 Hz, 2H),7.24-7.29 (m, 1 H), 7.17 (d, J=8.25 Hz, 2H), 7.01 (d, J=8.80 Hz, 2H),6.11 (dd, J=7.70, 2.20 Hz, 1 H), 6.07 (d, J=2.75 Hz, 1H), 4.53-4.66 (m,1H), 3.91 (app brs, 1H), 3.78-3.88 (m, 1H), 3.59-3.71 (m, 1H), 3.52-3.60(m, 1H), 3.10 (s, 3H), 2.50-2.64 (m, 2H), 2.09 (app brs, 2H), 1.80-1.98(m, 2H), 1.55-1.72 (m, 2H), 0.94 (t, J=7.42 Hz, 3 H). MS (ESI) 511(M+H).

Example 108 Preparation of4-(1-(5-methylpyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one,TFA salt

Example 108 was prepared according to procedures described in Example105 substituting methylboronic acid (Aldrich) for cyclopropylboronicacid except that the crude product was purified by preparative HPLC (C₁₈column, 10-100% MeOH in water containing 0.1% trifluoroacetic acid) togive Example 108 upon lyophilization. ¹H NMR (400 MHz, CD₃OD) δ ppm 8.30(s, 2H), 8.12 (d, J=8.31 Hz, 2H), 7.69 (d, J=8.80 Hz, 2H), 7.60 (d,J=7.83 Hz, 1H), 6.28 (dd, J=7.58, 2.69 Hz, 1H), 6.10 (d, J=2.45 Hz, 1H),4.78-4.85 (m, 1H), 4.12-4.20 (m, 2H), 3.68-3.77 (m, 2H), 3.18 (s, 3H),2.19 (s, 3H), 2.05-2.17 (m, 2H), 1.80-1.90 (m, 2H). MS (ESI) 441 (M+H).

Example 109 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(5-phenylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one,TFA salt

Example 109 was prepared according to procedures described in Example105 substituting phenylboronic acid (Aldrich) for cyclopropylboronicacid and substituting DMF for THF. Reaction was heated under microwavecondition at 120° C. for 10 min. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.56 (s,2H), 8.06 (d, J=8.80 Hz, 2H), 7.62 (d, J=8.80 Hz, 2H), 7.40-7.50 (m,4H), 7.31-7.38 (m, 1H), 7.23 (d, J=7.34 Hz, 1H), 6.07 (dd, J=7.83, 2.45Hz, 1H), 6.02 (d, J=2.93 Hz, 1H), 4.57-4.66 (m, 1H), 4.19-4.28 (m, 2H),3.70-3.80 (m, 2H), 3.08 (s, 3H), 2.05-2.15 (m, 2H), 1.83-1.94 (m, 2H).MS (ESI) 503 (M+H).

Example 110 Preparation of 4-cyanophenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 110 was prepared according to procedures described in Example 2substituting 4-hydroxybenzonitrile for 1,1,1-trifluoro-2-propanol atStep B. ¹H NMR (500 MHz, CDCl₃) δ 8.08 (d, J=8.25 Hz, 2H), 7.69 (d,J=8.80 Hz, 2H), 7.62 (d, J=8.80 Hz, 2H), 7.22-7.35 (m, 3H), 6.11 (dd,J=7.42, 2.47 Hz, 1H), 6.05 (d, J=2.75 Hz, 1H), 4.57-4.65 (m, 1H),3.86-3.95 (m, 1H), 3.76-3.86 (m, 1H), 3.63-3.72 (m, 1H), 3.55-3.64 (m,1H), 3.10 (s, 3H), 2.09 (app brs, 2H), 1.89-1.99 (m, 2H). MS (ESI) 494(M+H).

Example 111 Preparation of 2,2,2-trifluoroethyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 111 was prepared according to procedures described in Example 2substituting 2,2,2-trifluoroethanol for 1,1,1-trifluoro-2-propanol atStep B. ¹H NMR (500 MHz, CDCl₃) δ 8.09 (d, J=8.80 Hz, 2H), 7.61 (d,J=8.80 Hz, 2H), 7.31 (d, J=7.70 Hz, 1H), 6.29 (d, J=2.20 Hz, 1H), 6.20(dd, J=7.70, 2.75 Hz, 1H), 4.56-4.65 (m, 1H), 4.44-4.57 (m, 2H),3.71-3.83 (m, 2H), 3.46-3.58 (m, 2H), 3.11 (s, 3H), 2.02 (d app brs,2H), 1.86 (app brs, 2H). MS (ESI) 475 (M+H).

Example 112 Preparation of (1R,5R)-2,2,2-trifluoroethyl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate

Example 112 was prepared according to procedures described in Example 2substituting (3-exo)-tert-butyl3-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)-8-azabicyclo[3.2.1]octane-8-carboxylate(Example 25) for tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylateat Step A and 2,2,2-trifluoroethanol for 1,1,1-trifluoro-2-propanol atStep B. ¹H NMR (500 MHz, CDCl₃) δ 8.08 (d, J=8.80 Hz, 2 H), 7.61 (d,J=8.80 Hz, 2H), 7.20-7.32 (m, 1H), 6.24 (d, J=2.75 Hz, 1H), 6.09 (dd,J=7.70, 2.75 Hz, 1H), 4.73-4.87 (m, 1H), 4.54-4.67 (m, 1H), 4.39-4.55(m, 3H), 3.10 (s, 3H), 2.17-2.30 (m, 2H), 2.04-2.19 (m, 2H), 1.68-1.94(m, 4H). MS (ESI) 501 (M+H).

Example 113 Preparation of4-(1-(5,5′-bipyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 113 was prepared according to procedures described in Example109 substituting pyrimidin-5-ylboronic acid (Maybridge) forphenylboronic acid except that the crude solid was purified by flashchromatography (SiO₂, 0 to 10% MeOH in CH₂Cl₂) ¹H NMR (400 MHz, DMSO-d6)δ ppm 9.13 (s, 3H), 8.84 (s, 2 H), 8.03 (d, J=8.31 Hz, 2H), 7.69 (d,J=8.80 Hz, 2H), 7.65 (d, J=7.34 Hz, 1H), 6.05-6.14 (m, 2H), 4.76-4.86(m, 1H), 4.25-4.35 (m, 2H), 3.55-3.65 (m, 2H), 3.28 (s, 3H), 2.00-2.11(m, 2H), 1.58-1.69 (m, 2H). MS (ESI) 505 (M+H).

Example 114 Preparation of4-(1-(5-(4-chlorophenyl)pyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 114 was prepared according to procedures described in Example106 substituting 2-chloro-5-(4-chlorophenyl)pyrimidine (Peakdale) for2-chloro-5-propylpyrimidine in Step B. The reaction was heated undermicrowave conditions at 140-160° C. for 50 min. The crude solid waspurified by flash chromatography (SiO₂, 0 to 100% EtOAc in Hexanes). ¹HNMR (400 MHz, DMSO-d6) δ ppm 8.72 (s, 2H), 8.00-8.05 (m, 2H), 7.67-7.71(m, 4H), 7.65 (d, J=7.82 Hz, 1H), 7.40-7.55 (m, 2H), 6.07-6.13 (m, 2H),4.76-4.83 (m, 1H), 4.24-4.33 (m, 2H), 3.53-3.62 (m, 2 H), 3.28 (s, 3H),2.01-2.09 (m, 2H), 1.58-1.68 (m, 2H). MS (ESI) 537 (M+H).

Example 115 Preparation of4-(1-(5-bromopyridin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 115 was prepared according to procedures described in Example114 substituting 5-bromo-2-fluoropyridine (Aldrich) for2-chloro-5-(4-chlorophenyl)pyrimidine. ¹H NMR (400 MHz, CDCl₃) δ ppm8.20 (d, J=2.45 Hz, 1H), 8.04-8.09 (m, 2H), 7.59-7.64 (m, 2H), 7.56 (dd,J=9.05, 2.20 Hz, 1H), 7.23 (d, J=7.82 Hz, 1H), 6.62 (d, J=9.29 Hz, 1H),6.06 (dd, J=7.58, 2.69 Hz, 1H), 6.00 (d, J=2.45 Hz, 1H), 4.53-4.60 (m,1H), 3.84-3.92 (m, 2H), 3.41-3.52 (m, 2H), 3.09 (s, 3H), 2.05-2.14 (m,2H), 1.84-1.94 (m, 2H). MS (ESI) 504 (M+H).

Example 116 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(5-phenylpyridin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 116 was prepared according to procedures described in Example105 substituting4-(1-(5-bromopyridin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-onefor4-(1-(5-bromopyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one,substituting phenylboronic acid (Aldrich) for cyclopropylboronic acidand substituting DMF for THF. The reaction was heated under microwaveconditions at 120° C. for 10 min. ¹H NMR (400 MHz, DMSO-d6) δ ppm 8.37(d, J=2.45 Hz, 1H), 7.95 (d, J=8.31 Hz, 2 H), 7.77 (dd, J=9.05, 2.20 Hz,1H), 7.51-7.63 (m, 5H), 7.34 (t, J=7.58 Hz, 2H), 7.21 (t, J=7.82 Hz,1H), 6.90 (d, J=8.80 Hz, 1H), 5.98-6.04 (m, 2H), 4.65-4.73 (m, 1H),3.92-4.00 (m, 2H), 3.26-3.34 (m, 2H), 3.20 (s, 3H), 1.92-2.00 (m, 2 H),1.51-1.61 (m, 2H). MS (ESI) 502 (M+H).

Example 117 Preparation of isopropyl4-(2-oxo-1-(4-(2,2,2-trifluoroacetamido)phenyl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Step A. Preparation of isopropyl4-(1-(4-aminophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Isopropyl4-(1-(4-aminophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatewas prepared according to procedures described in Example 8 substitutingtert-butyl 4-iodophenylcarbamate for 4-bromobenzonitrile at Step C andthe cleavage of BOC protecting group occurred during the course of thereaction. MS (ESI) 372 (M+H).

Step B Example 117

A mixture of isopropyl4-(1-(4-aminophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(20 mg, 0.054 mmol), pyridine (0.022 mL, 0.269 mmol, EMD) andmethanesulfonyl chloride (0.013 mL, 0.162 mmol, Aldrich) in CH₂Cl₂ (0.5mL) was stirred at room temperature for 30 min and then evaporated underreduced pressure. The residue was purified by preparative HPLC (C₁₈column; 20-100% methanol in water containing 0.05% trifluoroacetic acid)to give Example 117 (12.4 mg, off-white solid, 49%) upon lyophilization.¹H NMR (500 MHz, CDCl₃) δ 9.72 (s, 1H), 7.55 (d, J=8.80 Hz, 2H),7.24-7.29 (m, 1H), 7.18 (d, J=8.80 Hz, 2 H), 6.05-6.24 (m, 2H),4.86-5.01 (m, 1H), 4.52-4.64 (m, 1H), 3.76 (app brs, 2 H), 3.37-3.52 (m,2H), 1.93-2.12 (m, 2H), 1.76-1.88 (m, 2H), 1.27 (d, J=6.05 Hz, 6H). MS(ESI) 468 (M+H).

Example 118 Preparation of isopropyl4-(1-(4-acetamidophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 118 was prepared according to procedures described in Example117 substituting acetyl chloride for methanesulfonyl chloride at Step B.¹H NMR (500 MHz, CDCl₃) δ 8.44 (d, J=7.70 Hz, 1H), 7.48 (d, J=8.25 Hz,2H), 7.29 (d, J=7.70 Hz, 1H), 7.18 (d, J=8.25 Hz, 2H), 6.25 (d, J=2.75Hz, 1H), 6.15 (dd, J=7.42, 2.47 Hz, 1H), 4.90-5.02 (m, 1H), 4.49-4.62(m, 1H), 3.76 (app brs, 2H), 3.34-3.48 (m, 2H), 2.14 (s, 3H), 1.93-2.07(m, 2H), 1.80 (app brs, 2H). MS (ESI) 449 (M+H).

Example 119 Preparation of isopropyl4-(1-(4-(3-methylureido)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 118 was prepared according to procedures described in Example117 substituting methylisocyanate for methanesulfonyl chloride at StepB. ¹H NMR (500 MHz, CDCl₃) δ 7.78 (brs, 1H), 7.23-7.29 (m, 1H),7.11-7.18 (m, 2H), 7.05-7.11 (m, 1H), 6.05-6.17 (m, 2H), 4.88-5.00 (m,1H), 4.51-4.60 (m, 1H), 3.68-3.81 (m, 2H), 3.36-3.50 (m, 2H), 2.79 (s,3H), 1.99 (app brs, 2H), 1.82 (app brs, 2 H), 1.27 (d, J=6.60 Hz, 6H).MS (ESI) 429 (M+H).

Example 120 Preparation of4-(1-(5-isopropylpyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one,TFA salt

Step A. Preparation of prop-1-en-2-ylboronic acid

To a stirring solution of prop-1-en-2-ylmagnesium bromide (0.5 N in THF,20 mL, 10.00 mmol, Aldrich) in THF (12.00 mL) at room temperature wasadded trimethyl borate (3.34 mL, 30.0 mmol, Aldrich). The reaction wasstirred at room temperature for 2.5 h and then cooled to 0° C. To thereaction was added hydrogen chloride (1 N in H₂O, 12 mL) and stirred for10 min. The resulting mixture was extracted with diethyl ether (2×20mL). The organic layers were combined, dried over Na₂SO₄, andconcentrated in vacuo to yield 600 mg of crude product as a white solid.

Step B. Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(5-(prop-1-en-2-yl)pyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

A mixture of4-(1-(5-bromopyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one(103 mg, 0.20 mmol), potassium carbonate (140 mg, 1.02 mmol, EMD) andprop-1-en-2-ylboronic acid (52.4 mg, 0.610 mmol) in DMF (1.8 mL) andWater (0.2 mL) was degassed by vacuum and purged with Argon. To theresulting mixture was added1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (16.72 mg, 0.020 mmol, Aldrich) and then heatedunder microwave conditions at 120° C. for 20 min. The reaction mixturewas concentrated in vacuo to a brown solid. The solid was purified byflash chromatography (SiO₂, 0 to 100% EtOAc in hexanes) to yield 25 mgof desired product as a light yellow solid. MS (ESI) 467 (M+H).

Step C. Example 120

A stirring suspension of1-(4-(methylsulfonyl)phenyl)-4-(1-(5-(prop-1-en-2-yl)pyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one(25 mg, 0.054 mmol) and palladium on activated carbon (20 mg, 10 wt. %,wet, Aldrich) in MeOH (10 mL) was placed under hydrogen (1 Atm) for 1 h.The resulting mixture was purged with Argon and then filtered through a45 μM syringe filter. The filtrate was concentrated in vacuo to a yellowoil. The oil was purified by preparative HPLC (C₁₈ column, 10-100% MeOHin water containing 0.1% trifluoroacetic acid) to yield 12.3 mg ofExample 120 as a white solid upon lyophilization ¹H NMR (400 MHz, CDCl₃)δ ppm 8.22 (s, 2H), 7.97-8.04 (m, 2H), 7.52-7.59 (m, 2H), 7.17 (d,J=7.34 Hz, 1H), 6.02 (dd, J=7.82, 2.45 Hz, 1H), 5.98 (d, J=2.45 Hz, 1H),4.48-4.60 (m, 1H), 4.04-4.15 (m, 2H), 3.59-3.72 (m, 2H), 3.03 (s, 3H),2.68-2.81 (m, 1H), 1.95-2.09 (m, 2H), 1.75-1.90 (m, 2H), 1.18 (d, J=6.85Hz, 6H). MS (ESI) 469 (M+H).

Example 121 Preparation of 4-butylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 110 was prepared according to procedures described in Example 2substituting 4-n-butylphenol for 1,1,1-trifluoro-2-propanol at Step B.¹H NMR (500 MHz, CDCl₃) δ 8.09 (d, J=8.25 Hz, 2H), 7.61 (d, J=8.80 Hz,2H), 7.37 (d, J=7.15 Hz, 1H), 7.17 (d, J=8.80 Hz, 2H), 7.00 (d, J=8.25Hz, 2H), 6.52 (d, J=2.75 Hz, 1 H), 6.31 (dd, J=7.70, 2.20 Hz, 1H),4.62-4.72 (m, 1H), 3.89-4.00 (m, 1H), 3.87 (app brs, 1H), 3.66 (app brs,1H), 3.56 (app brs, 1H), 3.11 (s, 3H), 2.53-2.66 (m, 2 H), 2.12 (appbrs, 2H), 1.88-1.98 (m, 2H), 1.52-1.64 (m, 2H), 1.27-1.42 (m, 2 H), 0.92(t, J=7.42 Hz, 3H). MS (ESI) 525 (M+H).

Example 122 Preparation of4-(1-(5-cyclohexenylpyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 122 was prepared according to procedures described in Example109 substituting cyclohexenylboronic acid (Combi-Phos) for phenylboronicacid. ¹H NMR (400 MHz, DMSO-d6) δ ppm 8.43 (s, 2H), 8.03 (d, J=8.31 Hz,2H), 7.68 (d, J=8.31 Hz, 2H), 7.64 (d, J=7.82 Hz, 1H), 6.02-6.15 (m,3H), 4.70-4.84 (m, 1H), 4.16-4.29 (m, 2H), 3.44-3.57 (m, 2H), 3.28 (s,3H), 2.25-2.35 (m, 2H), 2.09-2.19 (m, 2H), 1.93-2.07 (m, 2H), 1.65-1.76(m, 2H), 1.53-1.64 (m, 4H). MS (ESI) 507 (M+H).

Example 123 Preparation of biphenyl-4-yl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 123 was prepared according to procedures described in Example 2substituting biphenyl-4-ol for 1,1,1-trifluoro-2-propanol at Step B. ¹HNMR (500 MHz, CDCl₃) δ 8.08 (d, J=8.25 Hz, 2H), 7.63 (d, J=7.70 Hz, 2H),7.58 (t, J=7.97 Hz, 4H), 7.44 (t, J=7.42 Hz, 2H), 7.35 (t, J=6.87 Hz,1H), 7.24-7.28 (m, 1H), 7.19 (d, J=8.25 Hz, 2H), 6.09 (dd, 1H), 6.01 (d,J=2.75 Hz, 1H), 4.54-4.66 (m, 1H), 3.94 (app brs, 1H), 3.84 (app brs,1H), 3.67 (app brs, 1H), 3.69 (app brs, 1H), 3.10 (s, 3H), 2.10 (appbrs, 2H), 1.95 (app brs, 2H). MS (ESI) 555 (M+H).

Example 124 Preparation of 4-pentylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 124 was prepared according to procedures described in Example 2substituting 4-pentylphenol (Alfa Aesar) for 1,1,1-trifluoro-2-propanolat Step B. ¹H NMR (500 MHz, CDCl₃) δ d 8.10 (d, J=8.25 Hz, 2H), 7.61 (d,J=8.80 Hz, 2H), 7.38 (d, J=7.15 Hz, 1H), 7.17 (d, J=8.80 Hz, 2H), 7.00(d, J=8.25 Hz, 2H), 6.57 (d, J=2.20 Hz, 1H), 6.34 (dd, J=7.42, 2.47 Hz,1H), 4.62-4.75 (m, 1H), 3.79-4.03 (m, 2H), 3.62 (m, 2H), 3.12 (s, 3H),2.46-2.71 (m, 2H), 2.13 (app brs, 2H), 1.93 (m, 2H), 1.52-1.69 (m, 2H),1.22-1.44 (m, 4H), 0.89 (t, J=6.87 Hz, 3H). MS (ESI) 539 (M+H).

Example 125 Preparation of 4-ethoxyphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 125 was prepared according to procedures described in Example 2substituting 4-ethoxyphenol for 1,1,1-trifluoro-2-propanol at Step B. ¹HNMR (500 MHz, CDCl₃) δ 8.09 (d, J=8.80 Hz, 2H), 7.61 (d, J=8.80 Hz, 2H),7.35 (d, J=7.70 Hz, 1H), 7.01 (d, J=8.80 Hz, 2H), 6.87 (d, J=8.80 Hz,2H), 6.48 (d, J=2.20 Hz, 1 H), 6.29 (dd, J=7.70, 2.75 Hz, 1H), 4.61-4.72(m, 1H), 4.01 (q, J=6.78 Hz, 2H), 3.93 (app brs, 1H), 3.80-3.89 (m, 1H),3.60-3.70 (m, 1H), 3.55 (app brs, 1H), 3.11 (s, 3H), 2.12 (app brs, 2H),1.86-1.98 (m, 2H), 1.41 (t, J=6.87 Hz, 3H). MS (ESI) 513 (M+H).

Example 126 Preparation of 4-(trifluoromethoxy)phenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 126 was prepared according to procedures described in Example 2substituting 4-(trifluoromethoxy)phenol (Aldrich) for1,1,1-trifluoro-2-propanol at Step B. ¹H NMR (500 MHz, CDCl₃) 8.10 (d,J=8.25 Hz, 2H), 7.61 (d, J=8.80 Hz, 2 H), 7.38 (d, J=7.70 Hz, 1H), 7.23(d, J=8.80 Hz, 2H), 7.15 (d, J=8.80 Hz, 2H), 6.56 (d, J=2.75 Hz, 1H),6.33 (dd, J=7.70, 2.20 Hz, 1H), 4.61-4.78 (m, 1H), 3.90-4.01 (m, 1H)3.85 (app brs, 1H), 3.68 (app brs, 1H), 3.57 (app brs, 1H), 3.12 (s,3H), 2.13 (app brs, 2H), 1.87-1.99 (m, 2H). MS (ESI) 553 (M+H).

Example 127 Preparation of4-(1-(5-isobutylpyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 127 was prepared according to procedures described in Example120 Step B and C substituting 2-methylprop-1-enylboronic acid(Synthonix) for prop-1-en-2-ylboronic acid in Step B. The crude productwas purified by flash chromatography (SiO₂, 0 to 100% EtOAc in CH₂Cl₂)¹H NMR (400 MHz, CDCl₃) δ ppm 8.14 (s, 2H), 8.07 (d, J=8.31 Hz, 2H),7.62 (d, J=8.80 Hz, 2H), 7.23 (d, J=7.82 Hz, 1H), 6.07 (dd, J=7.82, 2.45Hz, 1H), 6.02 (d, J=2.45 Hz, 1H), 4.53-4.62 (m, 1 H), 4.14-4.24 (m, 2H),3.60-3.71 (m, 2H), 3.09 (s, 3H), 2.30 (d, J=7.34 Hz, 2H), 2.03-2.13 (m,2H), 1.81-1.90 (m, 2H), 1.70-1.80 (m, 1H), 0.91 (d, J=6.85 Hz, 6 H). MS(ESI) 483 (M+H).

Example 128 Preparation of isopropyl4-(2-oxo-1-(pyridin-2-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate,TFA salt

Example 128 was prepared according to procedures described in Example 8substituting 2-iodopyridine (TCI) for 4-bromobenzonitrile at Step C. ¹HNMR (400 MHz, DMSO-d₆). δ 8.56 (d, J=4.0 Hz, 1H), 7.94 (td, J=7.7, 1.7Hz, 1H), 7.82 (d, J=7.8 Hz, 1H), 7.74 (d, J=8.2 Hz, 1H), 7.44 (dd,J=6.8, 5.1 Hz, 1H), 6.09 (dd, J=7.8, 2.7 Hz, 1H), 5.99 (d, J=2.5 Hz,1H), 4.77 (spt, J=6.3 Hz, 1H), 4.63-4.71 (m, 1H), 3.64-3.74 (m, 2H),3.22 (t, J=10.0 Hz, 2H), 1.84-2.01 (m, 2H), 1.44-1.65 (m, 2H), 1.18 (d,J=6.3 Hz, 6H). MS (ESI) 358 (M+H).

Example 129 Preparation of4-(1-(5-ethylpyridin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one,TFA salt

Example 129 was prepared according to procedures described in Example116 substituting ethylboronic acid (Alfa Aesar) for phenylboronic acidexcept that the reaction was heated under microwave conditions at120-130° C. for 25 min and the crude product was purified by preparativeHPLC (C₁₈ column, 10-100% MeOH in water containing 0.1% trifluoroaceticacid) to yield 4.7 mg of Example 129 upon lyophilization ¹H NMR (400MHz, DMSO-d6) δ ppm 8.02 (d, J=8.80 Hz, 2H), 7.97 (s, 1H), 7.69 (d,J=8.31 Hz, 1H), 7.55 (d, J=8.80 Hz, 2H), 7.22 (d, J=7.34 Hz, 1H), 6.90(d, J=8.80 Hz, 1H), 6.06 (s, 1H), 6.04 (s, 1H), 4.59-4.70 (m, 1H),3.73-3.90 (m, 4H), 3.03 (s, 3H), 2.54 (q, J=7.66 Hz, 2H), 1.99-2.19 (m,4H), 1.18 (t, J=7.58 Hz, 3H). MS (ESI) 454 (M+H).

Example 130 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(5-(pyridin-4-yl)pyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 130 was prepared according to procedures described in Example113 substituting pyridin-4-ylboronic acid (Frontier Scientific) forpyrimidin-5-ylboronic acid. The resulting solid was washed with CH₂Cl₂in a final purification step. ¹H NMR (400 MHz, DMSO-d6) δ ppm 8.88 (s,2H), 8.56-8.62 (m, 2H), 7.99-8.08 (m, 2H), 7.67-7.75 (m, 4H), 7.65 (d,J=7.82 Hz, 1H), 6.10-6.14 (m, 1H), 6.09 (d, J=2.45 Hz, 1H), 4.78-4.86(m, 1H), 4.24-4.44 (m, 2H), 3.55-3.72 (m, 2 H), 3.29 (s, 3H), 1.99-2.15(m, 2H), 1.58-1.75 (m, 2H). MS (ESI) 504 (M+H).

Example 131 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(5-(pyridin-3-yl)pyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 131 was prepared according to procedures described in Example113 substituting pyridin-3-ylboronic acid (Frontier Scientific) forpyrimidin-5-ylboronic acid. ¹H NMR (400 MHz, DMSO-d6) δ ppm 8.89 (d,J=2.45 Hz, 1H), 8.78 (s, 2H), 8.53 (dd, J=4.65, 1.71 Hz, 1H), 8.05-8.10(m, 1H), 8.00-8.05 (m, 2H), 7.67-7.73 (m, 2H), 7.65 (d, J=7.34 Hz, 1H),7.43-7.49 (m, 1H), 6.10-6.15 (m, 1H), 6.09 (d, J=2.93 Hz, 1H), 4.76-4.86(m, 1H), 4.24-4.35 (m, 2H), 3.55-3.66 (m, 2H), 3.29 (s, 3H), 2.00-2.12(m, 2H), 1.57-1.71 (m, 2H). MS (ESI) 504 (M+H).

Example 132 Preparation of4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)-1-(pyridin-3-yl)pyridin-2(1H)-one,TFA salt

Step A. Preparation of tert-butyl4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

A stirring mixture of 4-hydroxypyridin-2(1H)-one (1.2 g, 10.8 mmol,prepared according to the procedure described at Step A of Example 8),tert-butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate (4.83 g, 17.3mmol, prepared according to the procedure described at Step C ofExample 1) and potassium carbonate (3.13 g, 22.7 mmol) in DMF (45 mL)was heated at 90° C. for 14 hrs and then cooled to room temperature. Theresulting mixture was diluted with EtOAc and H₂O and the aqueous layerwas extracted further with EtOAc (5×). The combined extracts were washedwith brine, dried (Na₂SO₄) and evaporated under reduced pressure. Theresidual was purified by flash chromatography on silica gel (0 to 10%MeOH/CH₂Cl₂) to yield 1.23 g (38.7%) of the product as a pinkish solid.MS (ESI) 295 (M+H).

Step B. Preparation of tert-butyl4-(2-oxo-1-(pyridin-3-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

A mixture of 3-iodopyridine (287 mg, 1.400 mmol, TCI), tert-butyl4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (206 mg,0.7 mmol), quinolin-8-ol (40.6 mg, 0.280 mmol, Alfa Aesar), copper(I)iodide (9.49 μL, 0.280 mmol, Aldrich) and cesium carbonate (296 mg,0.910 mmol, Aldrich) in DMSO (0.8 mL) was heated at 125° C. for 3 hrs.The reaction mixture was diluted with EtOAC and water and filtrated. Thefiltrate was separated and the aqueous layer was extracted further withEtOAc. The combined organic layers were washed with brine, dried(Na₂SO₄) and evaporated under reduced pressure. The residue was purifiedby flash chromatography on silica gel (0-10% MeOH/CH₂Cl₂) to give thetitle compound (165.7 mg, 64%) as a yellow solid. MS (ESI) 372 (M+H).

Step C. Preparation of4-(piperidin-4-yloxy)-1-(pyridin-3-yl)pyridin-2(1H)-one hydrochloricacid salt

A mixture of tert-butyl4-(2-oxo-1-(pyridin-3-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(142 mg, 0.382 mmol), hydrogen chloride (4.0 M in 1,4-dioaxne, 1.5 mL,Aldrich) in MeOH (1.5 mL) was stirred at room temperature for 45 min andthen concentrated to give the product (115 mg) as a light orange solid.The material was used in the next step without further purification. MS(ESI) 272 (M+H).

Step D Example 132

A mixture of 4-(piperidin-4-yloxy)-1-(pyridin-3-yl)pyridin-2(1H)-onehydrochloride (30.8 mg, 0.1 mmol), 2-chloro-5-propylpyrimidine (31.3 mg,0.200 mmol, Maybridge) and cesium carbonate (81 mg, 0.25 mmol, Aldrich)in DMF (0.6 mL) was heated under microwave conditions (160° C., 30 min).The reaction mixture was purified by preparative HPLC (C₁₈ column; 0-85%methanol in water containing 0.05% trifluoroacetic acid) to give Example132 (4.1 mg, off-white sticky solid, 10.5%) upon lyophilization. ¹H NMR(500 MHz, CDCl₃) δ 8.86 (s, 1H), 8.78 (d, J=4.40 Hz, 1H), 8.43 (s, 2H),8.22 (d, J=8.25 Hz, 1H), 7.78 (dd, J=7.97, 5.22 Hz, 1 H), 7.37 (d,J=7.70 Hz, 1H), 6.34 (d, J=2.20 Hz, 1H), 6.26 (dd, J=7.70, 2.75 Hz, 1H),4.67-4.82 (m, 1H), 3.95-4.19 (m, 4H), 2.55 (t, J=7.70 Hz, 2H), 2.01-2.22(m, 4H), 1.57-1.73 (m, 2H), 0.99 (t, J=7.42 Hz, 3H). MS (ESI) 292 (M+H).

Example 133 Preparation of4-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yloxy)-1-(pyridin-3-yl)pyridin-2(1H)-one,TFA salt

Example 133 was prepared according to procedures described in Example132 substituting 2-chloro-5-ethylpyrimidine (Aldrich) for2-chloro-5-propylpyrimidine at Step D. ¹H NMR (500 MHz, CDCl₃) δ 8.94(s, 1H), 8.81 (d, J=4.40 Hz, 1H), 8.43 (s, 2H), 8.31 (d, J=8.25 Hz, 1H),7.86 (dd, J=7.70, 5.50 Hz, 1 H), 7.42 (d, J=7.70 Hz, 1H), 6.38 (s, 1H),6.30 (dd, J=7.70, 2.75 Hz, 2H), 4.74-4.81 (m, 1H), 3.94-4.18 (m, 4H),2.63 (q, J=7.70 Hz, 2H), 2.01-2.23 (m, 4H), 1.28 (t, J=7.70 Hz, 3H). MS(ESI) 378 (M+H).

Example 134 Preparation of 4-tert-pentylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 134 was prepared according to procedures described in Example 2substituting 4-tert-pentylphenol (Aldrich) for1,1,1-trifluoro-2-propanol at Step B. ¹H NMR (500 MHz, CDCl₃) δ 8.09 (d,J=8.25 Hz, 2H), 7.62 (d, J=8.80 Hz, 2H), 7.29-7.33 (m, 3H), 7.03 (d,J=8.80 Hz, 2H), 6.25 (d, J=2.20 Hz, 1H), 6.19 (dd, J=7.70, 2.75 Hz, 1H),4.54-4.68 (m, 1H), 3.93 (app brs, 1H), 3.84 (app brs, 1H), 3.64 (appbrs, 1H), 3.55 (app brs, 1H), 3.11 (s, 3H), 2.10 (app brs, 2H),1.85-1.98 (m, 2H), 1.63 (q, J=7.70 Hz, 2H), 1.27 (s, 6H), 0.68 (t,J=7.42 Hz, 3H). MS (ESI) 539 (M+H).

Example 135 Preparation of 4-(trifluoromethyl)phenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 135 was prepared according to procedures described in Example 2substituting 4-(trifluoromethyl)phenol (Janssen) for1,1,1-trifluoro-2-propanol at Step B. ¹H NMR (500 MHz, CDCl₃) δ 8.09 (d,J=8.25 Hz, 2H), 7.63 (dd, J=14.30, 8.80 Hz, 4H), 7.35 (d, J=7.70 Hz,1H), 7.25 (d, J=8.25 Hz, 2H), 6.45 (d, J=2.75 Hz, 1H), 6.27 (dd, J=7.70,2.75 Hz, 1H), 4.63-4.72 (m, 1H), 3.89-3.99 (m, 1H), 3.85 (app brs, 1H),3.68 (app brs, 1H), 3.51-3.63 (m, 1H), 3.11 (s, 3H), 2.13 (app brs, 2H), 1.88-2.01 (m, 2H). MS (ESI) 537 (M+H).

Example 136 Preparation of 4-cyclopropylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Step A. Preparation of 4-bromophenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

To a mixture of1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloric acid (154 mg, 0.40 mmol) and diisopropylethylamine (0.35mL, 0.20 mmol) in CH₂Cl₂ (1.5 mL) at room temperature was added4-bromophenyl chloroformate (prepared according to procedures describedat Step B of Example 2 substituting 4-bromophenol for1,1,1-trifluoro-2-propanol) in CH₂Cl₂ (1.0 mL). The resulting mixturewas stirred at room temperature for 3 hrs, diluted with CH₂Cl₂ andwashed with water and brine. The organic layer was dried (Na₂SO₄) andevaporated under reduced pressure. The crude product was purified byflash chromatography on silica gel (0-100% EtOAc/Hexanes) to give thetitle compound (159 mg, 73%) as a light yellow solid. MS (ESI) 547, 549(M+H).

Step B Example 136

A mixture of 4-bromophenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(38.3 mg, 0.07 mmol),1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (5.76 mg, 7.00 μmol, Combiphos Catalysts, Inc.),cyclopropylboronic acid (18.04 mg, 0.210 mmol, Aldrich) and cesiumcarbonate (114 mg, 0.350 mmol, Aldrich) in DMF (0.5 mL) and water (0.1mL) was heated under microwave conditions (120° C., 20 min). Thereaction mixture was purified by preparative HPLC (C₁₈ column; 30-100%methanol in water containing 0.05% trifluoroacetic acid) to give Example136 (4.1 mg, beige color solid, 19%) upon lyophilization. ¹H NMR (500MHz, CDCl₃) δ 8.08 (d, J=8.80 Hz, 2H), 7.62 (d, J=8.25 Hz, 2H), 7.28 (d,J=7.15 Hz, 1H), 7.06 (d, J=8.80 Hz, 2H), 6.99 (d, J=8.80 Hz, 2H),6.12-6.19 (m, 2H), 4.53-4.67 (m, 1H), 3.91 (app brs, 1H), 3.83 (app brs,1H), 3.63 (app brs, 1H), 3.49-3.57 (m, 1H), 3.10 (s, 3H), 2.09 (app brs,2H), 1.81-1.99 (m, 3H), 0.94 (q, J=6.60 Hz, 2H), 0.59-0.73 (m, 2H). MS(ESI) 509 (M+H).

Example 137 Preparation of 4-(2-methylprop-1-enyl)phenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 137 was prepared according to procedures described in Example136 substituting 2-methylprop-1-enylboronic acid (Synthonix) forcyclopropylboronic acid at Step B. ¹H NMR (500 MHz, CDCl₃) δ 8.09 (d,J=8.25 Hz, 2H), 7.62 (d, J=8.25 Hz, 2H), 7.32 (d, J=7.70 Hz, 1H), 7.21(d, J=8.80 Hz, 2H), 7.05 (d, J=8.80 Hz, 2H), 6.33 (s, 1H), 6.19-6.26 (m,2H), 4.65 (d, J=3.30 Hz, 1H), 3.94 (app brs, 1H), 3.85 (app brs, 1H),3.65 (app brs, 1H), 3.56 (app brs, 1H), 3.11 (s, 3H), 2.11 (app brs,2H), 1.88-1.96 (m, 2H), 1.90 (s, 3H), 1.85 (s, 3H). MS (ESI) 523 (M+H).

Example 138 Preparation of 4-sec-butylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 138 was prepared according to procedures described in Example 2substituting 4-sec-butylphenol (Aldrich) for 1,1,1-trifluoro-2-propanolat Step B. ¹H NMR (500 MHz, CDCl₃) δ 8.09 (d, J=8.25 Hz, 2H), 7.61 (d,J=8.25 Hz, 2H), 7.37 (d, J=7.70 Hz, 1H), 7.17 (d, J=8.25 Hz, 2H), 7.02(d, J=8.25 Hz, 2H), 6.52 (d, J=2.20 Hz, 1H), 6.31 (dd, J=7.70, 2.20 Hz,1H), 4.64-4.72 (m, 1H), 3.97 (app brs, 1H), 3.85 (app brs, 1H), 3.66(app brs, 1H), 3.56 (app brs, 1H), 3.11 (s, 3H), 2.54-2.65 (m, 1H), 2.12(app brs, 2H), 1.86-1.96 (m, 2H), 1.53-1.63 (m, 2H), 1.22 (d, J=7.15 Hz,3H), 0.82 (t, J=7.42 Hz, 3H). MS (ESI) 525 (M+H).

Example 139 Preparation of 4-ethyl-2-methoxyphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 139 was prepared according to procedures described in Example 2substituting 4-ethyl-2-methoxyphenol (Alfa Aesar) for1,1,1-trifluoro-2-propanol at Step B. ¹H NMR (500 MHz, CDCl₃) δ 8.08 (d,J=8.25 Hz, 2H), 7.62 (d, J=8.80 Hz, 2H), 7.33 (d, J=7.70 Hz, 1H), 6.98(d, J=7.70 Hz, 1H), 6.74-6.80 (m, 2H), 6.36 (d, J=2.75 Hz, 1H), 6.24(dd, J=7.70, 2.75 Hz, 1H), 4.61-4.69 (m, 1H), 3.98 (app brs, 1H),3.79-3.87 (m, 1H), 3.84 (s, 3H), 3.67 (app brs, 1H), 3.55 (app brs, 1H),3.10 (s, 3H), 2.64 (q, J=7.70 Hz, 2H), 2.11 (app brs, 2H), 1.92 (appbrs, 2H), 1.24 (t, J=7.70 Hz, 3H). MS (ESI) 527 (M+H).

Example 141 Preparation of4-(1-(5-methoxypyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 141 was prepared according to procedures described in Example106 substituting 2-chloro-5-methoxypyrimidine (Aldrich) for2-chloro-5-propylpyrimidine in Step B except that the reaction wasstirred at 100° C. for 3 days and the crude solid was purified by flashchromatography (SiO₂, 0 to 100% EtOAc in Hexanes). ¹H NMR (400 MHz,DMSO-d6) δ ppm 8.20 (s, 2H), 7.98-8.06 (m, 2H), 7.65-7.73 (m, 2H), 7.63(d, J=7.34 Hz, 1H), 6.06-6.13 (m, 1H), 6.04 (d, J=2.45 Hz, 1H),4.67-4.79 (m, 1H), 4.07-4.20 (m, 2H), 3.76 (s, 3H), 3.35-3.47 (m, 2 H),3.27 (s, 3H), 1.94-2.04 (m, 2H), 1.49-1.64 (m, 2H). MS (ESI) 457 (M+H).

Example 142 Preparation of1-(2-fluoro-4-(methylsulfonyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one,hydrochloride salt

Step A. Preparation of 1-(5-propylpyrimidin-2-yl)piperidin-4-ol

A suspension of piperidin-4-ol (12 g, 119 mmol),2-chloro-5-propylpyrimidine (20.44 g, 131 mmol) and potassium carbonate(49.2 g, 356 mmol) in DMF (100 mL) was heated at 110° C. for 12 h. Themixture was diluted with EtOAc (250 ml) and washed three times withwater, dried over Na₂SO₄, and concentrated to give a yellow oil. The oilwas purified by flash chromatography (SiO₂, O-10% MeOH/CH₂Cl₂) to yieldproduct (19 g, 86 mmol, 72.4% yield) as yellow solid. MS (ESI) 222.2(M+1).

Step B. Preparation of 1-(5-propylpyrimidin-2-yl)piperidin-4-ylmethanesulfonate

To a mixture of 1-(5-propylpyrimidin-2-yl)piperidin-4-ol (16.1 g, 72.8mmol) and triethylamine (10.14 mL, 72.8 mmol) in CH₂Cl₂ (150 mL) at 0°C. was added methanesulfonyl chloride (4.76 mL, 80 mmol) slowly. Afterstirring at rt for 1.5 h, the mixture was quenched with 15 ml waterfollowed by 15 ml 1N HCl. The organic layer was collected and theaqueous layer was extracted with CH₂Cl₂. The combined organic layerswere then washed with saturated aqueous NaHCO₃ and brine. After dryingover Na₂SO₄, the organic layer was concentrated to give the desiredproduct 1-(5-propylpyrimidin-2-yl)piperidin-4-yl methanesulfonate (21 g,70.1 mmol, 96% yield) as yellow solid. MS (ESI) 300.2 (M+1).

Step C. Preparation of4-(benzyloxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)-pyridin-2(1H)-one

To 4-(benzyloxy)pyridin-2(1H)-one (6.12 g, 30.4 mmol) in a 500 mLrecovery flask was applied vacuum for 5 minutes then placed under anatmosphere of nitrogen and added DMF (100 mL) to produce a suspension.Added NaH (60% in oil) (1.271 g, 31.8 mmol) over 10 minutes as a slowevolution of gas was observed. By 60 minutes, the tan suspension hadbecome thicker and lighter in color. After 60 minutes added1,2-difluoro-4-(methylsulfonyl)benzene (5.31 g, 27.6 mmol) and placedthe reaction mixture in a 110° C. oil bath under nitrogen for 70 minutesto produce a tan suspension. Added 400 mL of water and 400 mL of EtOActo the reaction, removed aqueous layer, washed organic layer with 400 mLof brine, dried with MgSO₄, filtered and concentrated to give 12 g paleyellow powder. This was purified by flash chromatography (0.75-1.00%MeOH/CH₂Cl₂) followed by recrystallization from EtOAc to yield 5.39 g(14.4 mmol, 52% yield) of product as a white powder. MS (ESI) 374.4(M+1).

Step D. Preparation of1-(2-fluoro-4-(methylsulfonyl)phenyl)-4-hydroxypyridin-2(1H)-one

To a 1 liter recovery flask added 10% palladium on carbon (1.75 g, 16.44mmol), applied vacuum for 5 minutes then vented to nitrogen. Added 20 mLeach of CH₂Cl₂/MeOH/THF to wet solid, then added a suspension of4-(benzyloxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one(5.38 g, 14.41 mmol) in ˜80 mL each of CH₂Cl₂/MeOH/THF (total of 100 mLeach solvent), all while keeping a nitrogen flow over mixture. Appliedvacuum briefly then placed under an atmosphere of hydrogen for 105minutes, filtered through a 60×60 mm pad of CELITE® 545 filter aid usingan additional 200 mL each of MeOH and CH₂Cl₂, and concentrated thefiltrate to give 4.4 g of crude product as an off-white powder. MS (ESI)284.3 (M+1).

Step E. Example 142

To 1-(2-fluoro-4-(methylsulfonyl)phenyl)-4-hydroxypyridin-2(1H)-one (4.4g, 15.53 mmol) in a 200 mL recovery flask added 75 mL DMF, the mixturewas stirred 5 minutes to effect a partial solubilization, then1-(5-propylpyrimidin-2-yl)piperidin-4-yl methanesulfonate (6.9 g, 23.05mmol) was added and appeared to completely dissolve while some of thepyridone appeared to remain insoluble. Added cesium carbonate (15.18 g,46.6 mmol) and placed in a 90° C. oil bath under nitrogen for 225minutes to produce a brown-tan slurry. Added reaction mixture to 500 mLEtOAc then washed with water (250 mL then 3×150 mL), dried organic layerwith magnesium sulfate, filtered and then concentrated to give 8.7 gyellow solids which were purified by flash chromatography (50-100% EtOAcin hexane then 0-50% MeOH in EtOAc) to give 5.3 g (10.9 mmol) ofoff-white solid which were then recrystallized from EtOAc/hexane to givean electrostatic white solid. To this material were added 100 mL ofethanol to give a slurry to which was added 7.33 mL of 6 N aqueous HCl(44 mmol=4 equiv). Nearly all dissolved then a white precipitate beganto form. Stirred for 45 minutes then solvent was removed in vacuo togive 5.2 g of an off-white powder. Added 100 mL of ethanol and heated toreflux. The solids were only partially soluble. Let cool to rt withstirring. Filtered after 10 minutes at rt and washed the solids with2×10 mL of ethanol and 2×20 mL of hexane. Dried in vacuo to give Example142 (4.8 g, 9.1 mmol, 59%) as an off-white powder. ¹H NMR (500 MHz,CDCl₃) δ 0.98 (t, J=7.42 Hz, 3H) 1.60-1.70 (m, 2H) 2.07-2.20 (m, 4H)2.55 (t, J=7.42 Hz, 2H) 3.12 (s, 3H) 4.05-4.22 (m, 2H) 4.28-4.43 (m, 2H)4.73 (br. s., 1H) 6.06 (s, 1H) 6.11 (d, J=7.70 Hz, 1H) 7.18 (d, J=7.70Hz, 1H) 7.64 (t, J=7.15 Hz, 1H) 7.87 (t, J=8.80 Hz, 2H) 8.42 (s, 2H). MS(ESI) 487.6 (M+1).

Example 143 Preparation of 4-bromo-2-methylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 143 was prepared according to procedures described in Example 2substituting 4-bromo-2-methylphenol for 1,1,1-trifluoro-2-propanol atStep B. ¹H NMR (500 MHz, CDCl₃) δ 8.11 (d, J=8.80 Hz, 2H), 7.68 (d,J=8.80 Hz, 2H), 7.60 (d, J=7.70 Hz, 1H), 7.43 (d, J=1.65 Hz, 1H), 7.35(dd, J=8.52, 2.47 Hz, 1H), 6.98 (d, J=8.25 Hz, 1H), 6.29 (dd, J=7.70,2.75 Hz, 1H), 6.10 (d, J=2.75 Hz, 1H), 4.77-4.84 (m, 1H), 4.00 (app brs,1H), 3.83 (app brs, 1H), 3.70 (app brs, 1H), 3.49-3.57 (m, 1H), 3.18 (s,3H), 2.06-2.22 (m, 2H), 2.19 (s, 3H), 1.81-1.94 (m, 2H). MS (ESI) 561,563 (M+H).

Example 144 Preparation of 4-isobutylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

A suspension of 4-(2-methylprop-1-enyl)phenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(30 mg, 0.057 mmol) and palladium on carbon (10 wt. %, wet) (20 mg,0.188 mmol, Aldrich) in MeOH (4.0 mL) and DMF (0.5 mL) was placed underhydrogen (balloon) for 2 hrs and additional palladium on carbon (20 mg)was added. The resulting mixture was continuously stirred under hydrogen(balloon) for 1.5 hrs, diluted with CH₂Cl₂, filtrated through a pad ofCELITE® 545 filter aid and concentrated in vacuo. The residue waspurified by preparative HPLC (C₁₈ column; 30-100% methanol in watercontaining 0.05% trifluoroacetic acid) to give Example 144 (21.4 mg,yellow solid, 71%) upon lyophilization. ¹H NMR (500 MHz, CDCl₃) 8.10 (d,J=8.25 Hz, 2 H), 7.61 (d, J=8.25 Hz, 2H), 7.38 (d, J=7.70 Hz, 1H), 7.14(d, J=8.80 Hz, 2H), 7.00 (d, J=8.25 Hz, 2H), 6.56 (d, J=2.20 Hz, 1H),6.33 (dd, J=7.42, 2.47 Hz, 1H), 4.62-4.74 (m, 1H), 3.89-4.04 (m, 1H),3.85 (app brs, 1H), 3.85 (app brs, 1H), 3.57 (app brs, 1H), 3.12 (s,3H), 2.46 (d, J=7.15 Hz, 2H), 2.13 (app brs, 2H), 1.89-1.98 (m, 2H),1.80-1.89 (m, 1H), 0.90 (d, J=6.60 Hz, 6H). MS (ESI) 525 (M+H).

Example 145 Preparation of 4-bromo-2-fluorophenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 145 was prepared according to procedures described in Example 2substituting 4-bromo-2-fluorophenol (Aldrich) for1,1,1-trifluoro-2-propanol at Step B. ¹H NMR (500 MHz, CDCl₃) δ 8.07 (d,J=8.80 Hz, 2H), 7.62 (d, J=8.25 Hz, 2H), 7.33 (dd, J=9.35, 2.20 Hz, 1H),7.25-7.30 (m, 2H), 7.08 (t, J=8.52 Hz, 1H), 6.08 (dd, J=7.70, 2.75 Hz,1H), 5.99 (d, J=2.75 Hz, 1H), 4.56-4.65 (m, 1H), 3.84-3.96 (m, 1H),3.74-3.84 (m, 1H), 3.64-3.74 (m, 1H), 3.54-3.64 (m, 1H), 3.10 (s, 3H),2.08 (app brs, 2H), 1.95 (app brs, 2H). MS (ESI) 565, 567 (M+H).

Example 146 Preparation of 2-methoxy-4-propylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 146 was prepared according to procedures described in Example 2substituting 2-methoxy-4-propylphenol (SAFC) for1,1,1-trifluoro-2-propanol at Step B. ¹H NMR (500 MHz, CDCl₃) δ 8.09 (d,J=8.80 Hz, 2H), 7.62 (d, J=8.25 Hz, 2 H), 7.33 (d, J=7.15 Hz, 1H), 6.97(d, J=7.70 Hz, 1H), 6.71-6.79 (m, 2H), 6.37 (d, J=2.75 Hz, 1H), 6.25(dd, J=7.42, 2.47 Hz, 1H), 4.58-4.70 (m, 1H), 3.91-4.02 (m, 1H), 3.83(s, 3H), 3.77-3.88 (m, 1H), 3.61-3.71 (m, 1H), 3.55 (app brs, 1H), 3.11(s, 3H), 2.57 (t, J=7.70 Hz, 2H)), 2.12 (app brs, 2H), 1.93 (app brs,2H), 1.58-1.69 (m, 2H), 0.95 (t, J=7.42 Hz, 3H). MS (ESI) 541 (M+H).

Example 147 Preparation of 6-bromopyridin-3-yl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 147 was prepared according to procedures described in Example 2substituting 6-bromopyridin-3-ol (Synchem OHG) for1,1,1-trifluoro-2-propanol at Step B except that the title compound waspurified by flash chromatography on silica gel. ¹H NMR (500 MHz, CDCl₃)δ 8.23 (d, J=3.30 Hz, 1H), 8.08 (d, J=8.80 Hz, 2H), 7.62 (d, J=8.25 Hz,2H), 7.50 (d, J=8.25 Hz, 1H), 7.41 (dd, J=8.80, 2.75 Hz, 1H), 7.25 (d,J=7.24 Hz, 1H)), 6.09 (dd, J=7.70, 2.20 Hz, 1H), 6.00 (d, J=2.20 Hz,1H), 4.55-4.65 (m, 1H), 3.85-3.93 (m, 1H), 3.75-3.83 (m, 1H), 3.65-3.73(m, 1H), 3.55-3.63 (m, 1H), 3.10 (s, 3H), 2.02-2.14 (m, 2H), 1.91-2.00(m, 2H). MS (ESI) 548, 550 (M+H).

Example 148 Preparation of 2-methyl-4-propylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Step A. Preparation of (Z)-2-methyl-4-(prop-1-enyl)phenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

A mixture of 4-bromo-2-methylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(32.5 mg, 0.058 mmol, Example 143),1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (4.76 mg, 5.79 μmol, Combiphos Catalysts, Inc.),(Z)-prop-1-enylboronic acid (14.92 mg, 0.174 mmol, Aldrich) and cesiumcarbonate (94 mg, 0.289 mmol, Aldrich) in DMF (0.6 mL) and water (0.12mL) was heated under microwave conditions (100° C., 20 min). Thereaction mixture was purified by preparative HPLC (C₁₈ column; 40-100%methanol in water containing 0.05% trifluoroacetic acid) to give thetitle compound (21.8 mg, yellow solid, 72%) upon lyophilization. MS(ESI) 523 (M+H).

Step B Example 148

Example 148 was prepared according to procedures described in Example144 substituting (Z)-2-methyl-4-(prop-1-enyl)phenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatefor 4-(2-methylprop-1-enyl)phenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate.¹H NMR (500 MHz, CDCl₃) δ 8.10 (d, J=8.80 Hz, 2H), 7.62 (d, J=8.80 Hz,2H), 7.35 (d, J=7.70 Hz, 1H), 6.93-7.04 (m, 3H), 6.48 (d, J=2.75 Hz,1H), 6.29 (dd, J=7.70, 2.20 Hz, 1H), 4.64-4.71 (m, 1 H), 3.92-4.04 (m,1H), 3.81-3.92 (m, 1H), 3.68 (app brs, 1H), 3.56 (app brs, 1H), 3.12 (s,3H), 2.54 ((t, J=7.70 Hz, 2H), 2.07-2.22 (m, 2H), 2.19 (s, 3H), 1.93(app brs, 2H), 1.56-1.68 (m, 2H), 0.94 (t, J=7.15 Hz, 3H). MS (ESI) 525(M+H).

Example 149 Preparation of 2-fluoro-4-propylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 149 was prepared according to procedures described in Example148 substituting 4-bromo-2-fluorophenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatefor 4-bromo-2-methylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylateat Step A. ¹H NMR (500 MHz, CDCl₃) δ 8.09 (d, J=8.80 Hz, 2H), 7.62 (d,J=8.25 Hz, 2H), 7.32 (d, J=7.70 Hz, 1H), 7.07 (t, J=8.25 Hz, 1H),6.91-7.00 (m, 2H), 6.31 (d, J=2.47 Hz, 2H), 6.22 (dd, J=7.70, 2.20 Hz,1H), 4.60-4.72 (m, 1 H), 3.88-3.99 (m, 1H), 3.83 (app brs, 1H), 3.68(app brs, 1H), 3.57 (app brs, 1H), 3.11 (s, 3H), 2.50-2.61 (m, 2H), 2.11(app brs, 2H), 1.94 (app brs, 2H), 1.57-1.69 (m, 2H), 0.94 (t, J=7.15Hz, 3H). MS (ESI) 529 (M+H).

Example 150 Preparation of(Z)-1-(4-(methylsulfonyl)phenyl)-4-(1-(5-(prop-1-enyl)pyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 150 was prepared according to procedures described in Example109 substituting (Z)-prop-1-enylboronic acid (Aldrich) for phenylboronicacid except that the crude solid was purified by flash chromatography(SiO₂, 0 to 100% EtOAc in CH₂Cl₂). ¹H NMR (400 MHz, CDCl₃) δ ppm 8.31(s, 2H) 8.07 (d, J=8.31 Hz, 2H) 7.62 (d, J=8.31 Hz, 2H) 7.23 (d, J=7.34Hz, 1H) 6.17 (d, J=10.76 Hz, 1H) 6.05-6.10 (m, 1H) 6.02 (d, J=2.45 Hz,1H) 5.72-5.83 (m, 1H) 4.55-4.63 (m, 1H) 4.16-4.25 (m, 2H) 3.65-3.76 (m,2H) 3.09 (s, 3H) 2.02-2.14 (m, 2H) 1.88 (d, J=7.34 Hz, 3H) 1.80-1.86 (m,2H). MS (ESI) 467 (M+H).

Example 151 Preparation of4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one,TFA salt

Step A. Preparation of4-(1-(5-bromopyrimidin-2-yl)piperidin-4-yloxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

A mixture of1-(2-fluoro-4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloride (100 mg, 0.248 mmol, prepared according to the proceduresdescribed in Example 9), 5-bromo-2-chloropyrimidine (144 mg, 0.745 mmol)and cesium carbonate (324 mg, 0.993 mmol) in DMF (3 mL) was placed in amicrowave and heated at 160° C. for 20 min. The reaction mixture wasdiluted with EtOAc (30 mL) and washed with water 3 times. The organiclayer was dried over Na₂SO₄ and concentrated under reduced pressure togive a crude yellow solid. The residue was purified by flashchromatography (SiO₂, O-100% EtOAc/Hexanes) to give a white solid (70mg, 53.9%). MS (ESI) 523 (M+H).

Step B Example 151

To a microwave vial was added4-(1-(5-bromopyrimidin-2-yl)piperidin-4-yloxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one(70 mg, 0.134 mmol), cyclopropylboronic acid (34.5 mg, 0.401 mmol),1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (11.00 mg, 0.013 mmol) and K₂CO₃ (55.5 mg, 0.401mmol), DMF (2 mL) and water (0.5 mL). The mixture was heated at 125° C.in a microwave for 20 min. The mixture was diluted with EtOAc (20 mL)and washed with water (3×). The organic layer was collected andevaporated to give a yellow oil. The crude was purified by preparativeHPLC (C₁₈ column; 20-90% MeOH in water containing 0.1% trifluoroaceticacid) to give Example 151 (4.5 mg, 7%) as a white oil. ¹H NMR (500 MHz,CDCl₃) δ ppm 8.36 (s, 2H), 7.75-7.93 (m, 2H), 7.56-7.67 (m, 1H),7.18-7.25 (m, 1H), 6.43 (d, J=2.75 Hz, 1H), 6.25 (dd, J=7.70, 2.20 Hz,1H), 4.75-4.79 (m, 1H), 3.90-4.15 (m, 4H), 3.13 (s, 3H), 1.97-2.23 (m,4H), 1.73-1.92 (m, 1H), 0.97-1.16 (m, 2H), 0.57-0.83 (m, 2H). MS (ESI)485 (M+H).

Example 152 Preparation of 2-chloro-4-propylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Step A. Preparation of 4-bromo-2-chlorophenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

4-Bromo-2-chlorophenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatewas prepared according to procedures described in Example 2 substituting4-bromo-2-chlorophenol (Aldrich) for 1,1,1-trifluoro-2-propanol at StepB. MS (ESI) 581, 583 (M+H).

Step B Example 152

Example 152 was prepared according to procedures described in Example148 substituting 4-bromo-2-chlorophenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatefor 4-bromo-2-methylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylateat Step A. ¹H NMR (500 MHz, CDCl₃) δ 8.08 (d, J=8.80 Hz, 2H), 7.62 (d,J=8.80 Hz, 2H), 7.21-7.29 (m, 1H), 7.02-7.15 (m, 2H), 6.11 (dd, J=7.70,2.75 Hz, 1H), 6.04 (d, J=2.75 Hz, 1H), 4.55-4.68 (m, 1H), 3.96 (app brs,1H), 3.82 (app brs, 1H), 3.70 (app brs, 1H), 3.58 (app brs, 1H), 3.10(s, 3H), 2.49-2.62 (m, 2 H), 2.04-2.19 (m, 2H), 1.94 (app brs, 2H),1.55-1.70 (m, 2H), 0.94 (t, J=7.42 Hz, 3H). MS (ESI) 545 (M+H).

Example 153 Preparation of 6-propylpyridin-3-yl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate,TFA salt

Example 153 was prepared according to procedures described in Example148 substituting 6-bromopyridin-3-yl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(Example 147) for 4-bromo-2-methylphenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylateat Step A. ¹H NMR (500 MHz, CDCl₃) δ 8.63 (d, J=2.75 Hz, 1H), 8.08 (d,J=8.80 Hz, 2H), 7.76 (dd, J=8.80, 2.20 Hz, 1H), 7.62 (d, J=8.25 Hz, 2H),7.38 (d, J=8.80 Hz, 1H), 7.26 (d, J=7.70, 1H), 6.10 (dd, J=7.70, 2.75Hz, 1H), 6.02 (d, J=2.20 Hz, 1H), 4.57-4.68 (m, 1H), 3.84-3.95 (m, 1H),3.74-3.81 (m, 1H), 3.65-3.74 (m, 1H), 3.57-3.65 (m, 1H), 3.10 (s, 3H),2.92 (t, J=7.70 Hz, 2H), 2.04-2.15 (m 2H), 1.91-2.02 (m, 2H), 1.73-1.86(m, 2H), 1.00 (t, J=7.15 Hz, 3H). MS (ESI) 512 (M+H).

Example 154 Preparation of 4-(3,3,3-trifluoropropyl)phenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Step A. Preparation of(E)-1-(benzyloxy)-4-(3,3,3-trifluoroprop-1-enyl)benzene

A mixture of 4-(benzyloxy)phenylboronic acid (1026 mg, 4.50 mmol, AlfaAesar), (E)-1-bromo-3,3,3-trifluoroprop-1-ene (262 mg, 1.5 mmol,SynQuest), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloridedichloromethane complex (122 mg, 0.15, Combiphos Catalysts, Inc.) andcesium carbonate (2444 mg, 7.50 mmol, Aldrich) in Water (0.5 mL) and DMF(3.0 mL) was heated under microwave conditions (90° C., 20 min). Thereaction mixture was diluted with EtOAc and filtered. The filtrate waswashed with water and brine, dried (Na₂SO₄) and concentrated in vacuo.The residual was purified by flash chromatography on silica gel (0 to100% EtOAc/hexanes) to yield the title compound (310 mg, 74%) as a paleyellow solid.

Step B. Preparation of 4-(3,3,3-trifluoropropyl)phenol

A solution of (E)-1-(benzyloxy)-4-(3,3,3-trifluoroprop-1-enyl)benzene(305 mg, 1.096 mmol) and palladium on carbon (305 mg, 10 wt. %, wet,Aldrich) in MeOH (15 mL) and THF (5 mL) was placed under hydrogen (1Atm) for 4 hrs. The resulting mixture was diluted with CH₂Cl₂ andfiltered through a pad of CELITE® 545 filter aid. The filtrate wasevaporated under reduced pressure and then purified by flashchromatography on silica gel (0 to 30% EtOAc/hexanes) to yield the titlecompound (151 mg, 72%) as a colorless oil. MS (ESI) 189 (M−H).

Step C Example 154

Example 154 was prepared according to procedures described in Example 2substituting 4-(3,3,3-trifluoropropyl)phenol for1,1,1-trifluoro-2-propanol at Step B. ¹H NMR (500 MHz, CDCl₃) δ 8.10 (d,J=8.80 Hz, 2H), 7.62 (d, J=8.80 Hz, 2H), 7.33 (d, J=7.70 Hz, 1H), 7.20(d, J=8.25 Hz, 2H), 7.06 (d, J=8.25 Hz, 2H), 6.40 (d, J=2.75 Hz, 1H),6.25 (dd, J=7.70, 2.75 Hz, 1H), 4.59-4.71 (m, 1H), 3.94 (app brs, 1H),3.79-3.91 (m, 1H), 3.60-3.71 (m, 1H), 3.51-3.60 (m, 1H), 3.11 (s, 3H),2.81-2.94 (m, 2H), 2.29-2.47 (m, 2H), 2.11 (app brs, 2H), 1.84-1.98 (m,2H). MS (ESI) 565 (M+H).

Example 155 Preparation of1-(4-(methylthio)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Step A. Preparation of benzyl4-(methylsulfonyloxy)piperidine-1-carboxylate

To a stirring solution of benzyl 4-hydroxy-1-piperidinecarboxylate (3.55mL, 23.4 mmol, Aldrich) and Et₃N (7.18 mL, 51.5 mmol, Aldrich) in CH₂Cl₂(25 mL) at room temperature was added a solution of methanesulfonylchloride (1.99 mL, 25.8 mmol, Acros) in CH₂Cl₂ (25 mL) dropwise. Thereaction mixture was stirred at room temperature for 1 h and washed with1N HCl aqueous solution, H₂O and brine. The organic layer was dried overNa₂SO₄ and concentrated in vacuo to yield 7.43 g of the desired productas a yellow oil. MS (ESI) 314 (M+H).

Step B. Preparation of benzyl4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

A stirring suspension of benzyl4-(methylsulfonyloxy)piperidine-1-carboxylate (1.97 g, 6.30 mmol),4-hydroxypyridin-2(1H)-one (0.50 g, 4.5 mmol, Aldrich), potassiumcarbonate (1.43 g, 10.6 mmol, EMD) and DMF (25 mL) was heated at 140° C.for 2.5 h and then cooled to room temperature. The resulting mixture wasdiluted with H₂O and extracted with EtOAc (2×). The organic layers werecombined and washed with brine, dried over Na₂SO₄ and concentrated invacuo to a light yellow oil. The oil was purified by flashchromatography (SiO₂, 0 to 10% MeOH in CH₂Cl₂) to yield 550 mg ofdesired product as a white solid. MS (ESI) 329 (M+H).

Step C. Preparation of benzyl4-(1-(4-(methylthio)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

A mixture of benzyl4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (697 mg,2.12 mmol), (4-bromophenyl)(methyl)sulfane (431 mg, 2.12 mmol, Aldrich),quinolin-8-ol (61.6 mg, 0.425 mmol, Alfa Aesar), potassium carbonate(381 mg, 2.76 mmol, EMD), Copper(I) iodide (81 mg, 0.43 mmol, AlfaAesar) in DMSO (6 mL) was stirred at 145° C. overnight under Argon. Theresulting mixture was diluted with H₂O and extracted with EtOAc (2×).The combined organic layers were washed with brine, dried over Na₂SO₄and concentrated in vacuo to a green solid. The solid was purified byflash chromatography (SiO₂, 0 to 5% MeOH in CH₂Cl₂) to yield 911 mg ofdesired product as a light green solid. MS (ESI) 451 (M+H).

Step D. Preparation of1-(4-(methylthio)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-one

To a stirring solution of benzyl4-(1-(4-(methylthio)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(367 mg, 0.815 mmol) in CH₂Cl₂ (5 mL) at 0° C. was addediodotrimethylsilane (0.33 mL, 2.4 mmol, Aldrich). The reaction wasstirred for 40 min and then quenched at 0° C. with HCl (1N in H₂O, 5mL). To the resulting mixture was diluted with CH₂Cl₂ and extracted withH₂O. The H₂O layer was basified with NaOH (1N in H₂O, 10 mL) andextracted with CH₂Cl₂ (2×). The combined organic layers were washed withbrine, dried over Na₂SO₄ and concentrated in vacuo to yield 189 mg crudeproduct as an off-white solid. MS (ESI) 317 (M+H).

Step E Example 155

To a stirring mixture of1-(4-(methylthio)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-one (175 mg,0.552 mmol) and potassium carbonate (305 mg, 2.21 mmol, EMD) in DMF (8.5mL) was added at room temperature 2-chloro-5-propylpyrimidine (130 mg,0.828 mmol, Wako). The reaction mixture heated at 100° C. for 9 h andthen concentrated in vacuo. The obtained oil was purified by flashchromatography (SiO₂, 0 to 100% EtOAc in CH₂Cl₂) to yield 101 mg ofexample 155 as a white solid. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.14 (s,2H), 7.25-7.36 (m, 4 H,) 7.18 (d, J=7.34 Hz, 1H,) 5.82-6.18 (m, 2H),4.46-4.58 (m, 1H), 4.12-4.23 (m, 2H), 3.53-3.66 (m, 2H), 2.49 (s, 3H),2.38 (t, J=7.58 Hz, 2H), 2.00-2.14 (m, 2H), 1.73-1.89 (m, 2H), 1.46-1.63(m, 2H), 0.92 (t, J=7.34 Hz, 3H). MS (ESI) 437 (M+H).

Example 156 Preparation of(±)-1-(4-(methylsulfinyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

To a stirring solution of1-(4-(methylthio)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one(51.4 mg, 0.118 mmol) in CH₂Cl₂ (15 mL) at 0° C. was added a solution of3-Chloroperoxybenzoic acid (26.4 mg, 0.118 mmol) in 5 mL CH₂Cl₂. Thereaction was stirred at 0° C. for 15 min and then quenched with Na₂SO₃(sat. solution in H₂O). The organic layer was washed with H₂O, brine,dried over Na₂SO₄ and concentrated in vacuo to a white solid. The solidwas purified by flash chromatography (SiO₂, 0 to 10% MeOH in CH₂Cl₂) toyield 50 mg of desired product as a white solid. ¹H NMR (400 MHz, CDCl₃)δ ppm 8.16 (s, 2H), 7.77 (d, J=8.31 Hz, 2H), 7.57 (d, J=8.31 Hz, 2H),7.23 (d, J=7.34 Hz, 1H), 5.94-6.11 (m, 2H), 4.44-4.64 (m, 1H), 4.07-4.31(m, 2H), 3.50-3.74 (m, 2 H), 2.77 (s, 3H), 2.40 (t, J=7.58 Hz, 2H),1.98-2.17 (m, 2H), 1.73-1.93 (m, 2H), 1.50-1.64 (m, 2H), 0.93(t_(r)=7.34 Hz, 3H). MS (ESI) 453 (M+H).

Example 157 Preparation of 4-(2-fluoroethyl)phenyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 157 was prepared according to procedures described in Example154 substituting (E)-1-bromo-2-fluoroethene (SynQuest) for(E)-1-bromo-3,3,3-trifluoroprop-1-ene at Step A. ¹H NMR (500 MHz, CDCl₃)δ 8.08 (d, J=8.80 Hz, 2H), 7.62 (d, J=8.80 Hz, 2H), 7.20-7.29 (m, 3H),7.06 (d, J=8.25 Hz, 2H), 6.09 (dd, J=7.70, 2.20 Hz, 1H), 6.00 (d, J=2.20Hz, 1H), 4.67 (t, J=6.32 Hz, 1H), 4.62 4.65 (m, 2H), 3.91 (app brs, 1H),3.78-3.85 (m, 1H), 3.62-3.69 (m, 1H), 3.53-3.60 (m, 1H), 3.10 (s, 3H),3.04 (t, J=6.60 Hz, 1H), 2.99 (t, J=6.32 Hz, 1H), 2.03-2.13 (m, 2H),1.87-1.97 (m, 2H). MS (ESI) 515 (M+H).

Example 158 Preparation of benzyl4-(5-methyl-1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Step A. Preparation of benzyl4-(methylsulfonyloxy)piperidine-1-carboxylate

To benzyl 4-hydroxypiperidine-1-carboxylate (48.8 g, 207 mmol) in CH₂Cl₂(400 mL) was added triethylamine (57.8 mL, 415 mmol), the mixture wascooled to 0° C. under nitrogen and then methanesulfonyl chloride (17.78mL, 228 mmol) was added over 15 minutes keeping internal temperaturebelow 30° C. After 2 hours at 0° C., the reaction was quenched with 300mL of 0.1 N aqueous HCl, the organic layer was washed with 300 mL ofwater, 300 mL of brine, dried with MgSO₄, filtered and concentrated togive the product (69.5 g) as an amber liquid which was used withoutfurther purification. MS (ESI) 314.4 (M+1).

Step B. Preparation of 6-chloro-4-hydroxy-5-methylpyridin-2(1H)-one

Malonyl dichloride (25 g, 177 mmol) was added to propiononitrile (30 mL,420 mmol) at rt under argon. The reaction mixture was stirred at rtovernight. 1,4-dioxane (50 mL) was added to the above heterogeneousmixture to yield a precipitate which was collected by filtration, washedwith 1,4-dioxane (2×20 mL) and dried in vacuum oven at 55° C. for 4 h toprovide 6-chloro-4-hydroxy-5-methylpyridin-2(1H)-one, HCl, H₂O (15.6 g,73 mmol, 34%) as an off-white solid. MS (ESI) 314.4 (M+1).

Step C. Preparation of 4-hydroxy-5-methylpyridin-2(1H)-one

6-Chloro-4-hydroxy-5-methylpyridin-2(1H)-one, HCl, H₂O (1 g, 4.67 mmol)was dissolved in 30 mL EtOH, and then triethylamine (0.473 g, 4.67 mmol)was added. The reaction was flushed with vacuum and then hydrogen threetimes, then placed under a balloon of hydrogen for 50 hours. Thereaction mixture was passed through a 20×20 mm pad of CELITE® 545 filteraid using an additional 4×5 mL of EtOH and the eluant was concentratedto 1.62 g of a tan foam. Added 20 mL of water, heated to reflux causingnearly all to dissolve, then let cool to rt. Filtered the suspensionfrom above and washed with 3×3 mL of water, and dried in vacuo toproduct (97 mg, 0.8 mmol, 17%) as a pale tan powder. MS (ESI) 126.1(M+1).

Step D. Preparation of benzyl4-(5-methyl-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

4-Hydroxy-5-methylpyridin-2(1H)-one (554 mg, 4.43 mmol), benzyl4-(methylsulfonyloxy)piperidine-1-carboxylate (2081 mg, 6.64 mmol), andpotassium carbonate (1224 mg, 8.86 mmol) were stirred in DMF (12 mL) at100° C. under nitrogen for 14 hours. 100 mL water and 100 mL EtOAc wasadded and then washed the EtOAc layer with 2×100 mL additional water.The organic layer was dried with Na₂SO₄, filtered, and concentrated togive 1454 mg of a brown oil. The oil was purified by flashchromatography (0-5% MeOH/CH₂Cl₂) to give product (280 mg, 0.82 mmol,18%) as a pale tan foam. MS (ESI) 343.4 (M+1).

Step E. Example 158

Benzyl4-(5-methyl-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(34 mg, 0.099 mmol), 4-bromophenyl methylsulphone (23.35 mg, 0.099mmol), potassium carbonate (20.59 mg, 0.149 mmol), and copper(I) iodide(3.78 mg, 0.020 mmol) were combined in 0.4 mL DMSO was degassed withbubbling nitrogen subsurface for 20 seconds and then heated in a 100° C.oil bath for 16 hours. To the reaction mixture was added 5 mL EtOAcwhich was then washed with 3 mL each of saturated aqueous NH₄Cl, NaHCO₃,NaCl, water, dried with MgSO₄ and filtered. The EtOAc filtrate was thenpurified directly with flash chromatography (EtOAc as eluant) to yieldproduct (24 mg, 0.048 mmol, 49%) as a yellow foam. ¹H NMR (500 MHz,CDCl₃) δ 1.81-1.93 (m, 2H) 1.92-2.00 (m, 2H) 2.02 (s, 3H) 3.09 (s, 3H)3.48-3.63 (m, 2H) 3.66-3.78 (m, 2H) 4.58 (br. s., 1H) 5.16 (s, 2H) 5.96(br. s., 1 H) 7.10 (br. s., 1H) 7.30-7.45 (m, 5H) 7.61 (d, J=8.25 Hz,2H) 8.06 (d, J=8.25 Hz, 2H). MS (ESI) 497.6 (M+1).

Example 159 Preparation of(±)-4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfinyl)phenyl)pyridin-2(1H)-one

Step A. Preparation of 2-chloro-5-cyclopropylpyrimidine

A mixture of 5-bromo-2-chloropyrimidine (100 mg, 0.517 mmol, Aldrich),cyclopropylboronic acid (57.7 mg, 0.672 mmol, Aldrich),Tricyclohexylphosphine (14.50 mg, 0.052 mmol, Aldrich) and K₃PO₄ (384mg, 1.81 mmol, EMD) in Toluene (2 mL) and Water (0.110 mL) was degassedby vacuum and purged with Ar. To the resulting mixture was addedPalladium(II) acetate (5.80 mg, 0.026 mmol, Stem) and then heated undermicrowave conditions at 120° C. for 10 min. The reaction mixture wasquenched with H₂O and then extracted with EtOAc (2×). The combinedorganic layers were washed with brine, dried over Na₂SO₄ andconcentrated in vacuo to a yellow oil. The oil was purified by flashchromatography (SiO₂, 0 to 20% EtOAc in Hexanes) to yield 71 mg of thedesired compound as a white solid. MS (ESI) 155 (M+H).

Step B Example 159

Example 159 was prepared according to procedures described in Example155 and 156 substituting 2-chloro-5-cyclopropylpyrimidine for2-chloro-5-propylpyrimidine in Example 155 step E. ¹H NMR (400 MHz,CDCl₃) δ ppm 8.13 (s, 2H), 7.77 (d, J=8.31 Hz, 2H), 7.57 (d, J=8.31 Hz,2H), 7.23 (d, J=7.34 Hz, 1H), 6.04-6.09 (m, 1H), 5.98-6.03 (m, 1H),4.51-4.62 (m, 1H), 4.12-4.24 (m, 2H), 3.56-3.68 (m, 2H), 2.77 (s, 3H),1.98-2.13 (m, 2H), 1.77-1.89 (m, 2H), 1.66-1.77 (m, 1H), 0.86-0.95 (m,2H), 0.53-0.65 (m, 2H). MS (ESI) 451 (M+H).

Example 160 Preparation of4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-5-methyl-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Step A. Preparation of5-methyl-1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-one

To a suspension of 10% Pd/C (100 mg, 0.940 mmol) in 5 mL MeOH undernitrogen was added Example 158 (218 mg, 0.439 mmol), flushed with vacuumthen hydrogen three times, then placed under a balloon of hydrogen for150 minutes. The reaction passed through a 15 mm id×30 mm CELITE® 545filter aid plug eluting with 15 mL of additional MeOH. Concentrated thefiltrate to 135 mg of a pale yellow-grey foam. MS (ESI) 363.2 (M+1).

Step B Preparation of Example 160

To the compound from Step A above (30 mg, 0.083 mmol),2-chloro-5-cyclopropylpyrimidine (25.6 mg, 0.166 mmol), and potassiumcarbonate (11.44 mg, 0.083 mmol) were added in 0.3 mL DMF and thenheated in a 100° C. oil bath for 15.5 hours. To the reaction mixture wasadded 2 mL EtOAc and then washed with 2 mL each of saturated aqueousNH₄Cl, NaHCO₃, NaCl, and water. The EtOAc layer was passed through a 4mm id×25 mm silica column eluting with ˜7 mL EtOAc. Concentrated eluateto 38 mg pale yellow oil which was crystallized from EtOAc to yieldExample 160 (17 mg, 0.034 mmol, 42%) as an off-white solid. ¹H NMR (500MHz, CDCl₃) δ ppm 0.51-0.66 (m, 2H) 0.86-0.97 (m, 2H) 1.65-1.81 (m, 2H)1.83-1.95 (m, 3H) 1.96-2.14 (m, 6H) 3.09 (s, 3H) 3.71-3.88 (m, 2H)3.99-4.11 (m, 2H) 4.55-4.70 (m, 1H) 6.00 (s, 1H) 7.07 (s, 1H) 7.63 (d,J=8.80 Hz, 2H) 8.06 (d, J=8.80 Hz, 2H) 8.15 (s, 2H). MS (ESI) 481.3(M+1).

Example 161 Preparation of tert-butyl4-(5-methyl-1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

The compound obtained in Example 160, Step A (30 mg, 0.083 mmol) wasdissolved in dichloromethane (0.5 mL) andN-ethyl-N-isopropylpropan-2-amine (0.022 mL, 0.124 mmol) and DMAP (1.011mg, 8.28 nmol)was added followed by di-tert-butyl dicarbonate (19.87 mg,0.091 mmol). The mixture was stirred at rt for 16 hours. To the reactionwas added 2 mL CH₂Cl₂ then the mixture was washed with 2 mL each ofsaturated aqueous NH₄Cl, NaHCO₃, NaCl, and 2 mL of water. The organiclayer was passed through a 4 mm id×25 mm silica column eluting with ˜5mL CH₂Cl₂ then 5 mL 5% CH₃OH/CHCl₃. Concentration of the 5 mL 5%CH₃OH/CHCl₃ provided Example 161 (34 mg, 0.074 mmol, 89%) as a paleyellow solid. ¹H NMR (500 MHz, CDCl₃) δ ppm 1.46 (s, 9H) 1.77-1.89 (m,2H) 1.92-2.09 (m, 5 H) 3.09 (s, 3H) 3.33-3.52 (m, 2H) 3.57-3.71 (m, 2H)4.48-4.63 (m, 1H) 5.98 (br. s., 1H) 7.09 (s, 1H) 7.61 (d, J=8.25 Hz, 2H)8.05 (d, J=8.80 Hz, 2H). MS (ESI) 463.3 (M+1).

Example 162 Preparation of4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-6-methyl-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Step A. Preparation of tert-butyl4-(6-methyl-1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

The intermediate was prepared according to procedures described inExample 1 substituting 4-hydroxy-6-methylpyridin-2(1H)-one for4-(benzyloxy)pyridin-2(1H)-one in Step A. MS (ESI) 463 (M+H).

Step B. Preparation of6-methyl-1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloride

The compound was prepared according to procedures described in Example 2substituting tert-butyl4-(6-methyl-1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatefor tert-butyl4-(1-(4-(methylsulfononyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatein Step A. MS (ESI) 363 (M+H).

Step C Example 162

A mixture of6-methyl-1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloride (44 mg, 0.110 mmol), 2-chloro-5-cyclopropylpyrimidine (20mg, 0.129 mmol) and cesium carbonate (180 mg, 0.552 mmol) in DMF (0.5mL) was placed in a closed vial and stirred at 120° C. for 10 h. Thereaction mixture was diluted with EtOAc (20 mL) and washed with water 3times. The organic layer was then dried (Na₂SO₄) and evaporated underreduced pressure to give a yellow solid. The residue was purified byflash chromatography (SiO₂, O-100% EtOAc/Hexanes) to give Example 162(16 mg, 30.2% yield) as a white solid. ¹H NMR (500 MHz, CDCl₃) δ ppm8.03-8.17 (m, 4H), 7.44 (d, J=8.80 Hz, 2H), 5.91 (s, 2H), 4.48-4.58 (m,1H), 4.10-4.22 (m, 2H), 3.62 (ddd, J=13.20, 8.80, 3.85 Hz, 2H), 3.12 (s,3H), 1.96-2.13 (m, 2H), 1.90 (s, 3H), 1.75-1.86 (m, 2 H), 1.67-1.76 (m,1H), 1.62 (s, 4H), 0.81-0.96 (m, 2H), 0.47-0.64 (m, 2H). MS (ESI) 481(M+H).

Example 163 Preparation of5-methyl-1-(4-(methylsulfonyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one,hydrochloride salt

The compound obtained in Example 160, Step A (25 mg, 0.069 mmol) and2-chloro-5-propylpyrimidine (12.96 mg, 0.083 mmol) were dissolved in DMF(0.3 mL), potassium carbonate (38.1 mg, 0.276 mmol) was added and themixture placed in a 100° C. oil bath for 115 minutes. To the reactionwas added 2 mL EtOAc and then washed successively with 2 mL each ofsaturated aqueous NH₄Cl, NaHCO₃, NaCl, and water. The reaction was driedwith MgSO₄, filtered and concentrated to 31 mg of tan solids. To the 31mg of solids were added 0.6 mL EtOH and then 30 uL of 6 N aqueous HCl(0.18 mmol=2.6 equiv) causing complete solution. The solvent was removedin vacuo to provide 38 mg of a pale tan foam. This material readilydissolved in 0.6 mL EtOH. To this solution, hexane was added in 30 uLincrements until 180 uL was added at which point cloudiness was observedand then a precipitate formed. The mixture was heated to reflux but onlypartial solubilization occurred. After stirring at rt overnight, themixture was filtered and washed with EtOH (0.3 mL) then 2×1 mL hexane toprovide Example 163 (22 mg, 0.042 mmol, 61%) as a white powder. ¹H NMR(500 MHz, methanol-d₃) δ ppm 1.01 (t, J=7.42 Hz, 3H) 1.18 (t, J=7.15 Hz,1H) 1.57-1.77 (m, 2H) 2.02-2.18 (m, 5H) 2.18-2.36 (m, 2H) 2.49-2.71 (m,2H) 3.19 (s, 3H) 4.07 (t, J=5.50 Hz, 4H) 4.97-5.10 (m, 1H) 6.29 (s, 1H)7.64 (s, 1H) 7.72 (d, J=8.25 Hz, 2H) 8.14 (d, J=8.80 Hz, 2H) 8.53 (s,2H). MS (ESI) 483.5 (M+1).

Example 164 Preparation of isopropyl4-(5-methyl-1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

The compound obtained in Example 160, Step A (25 mg, 0.069 mmol) wasdissolved in dichloromethane (0.5 mL) to which was then addedtriethylamine (0.029 mL, 0.207 mmol) and isopropyl carbonochloridate(10.1 mg, 0.083 mmol). After 45 minutes the solvent was removed in vacuoand the residue purified by passing through a UCT (United ChemicalTechnologies) 2.5 g C-18 cartridge (#CEC181(2500)₆) and eluting asfollows:

Fraction Volume Solvent 1 25 mL water 2 25 mL 30% MeOH/water 3-5  8 mL100% MeOHFraction 3 was concentrated in vacuo to give Example 164 (24 mg, 0.052mmol, 76%) as a tan foam. ¹H NMR (500 MHz, methanol-d₃) δ ppm 1.27 (d,J=6.05 Hz, 6H) 2.02 (dd, J=8.52, 4.12 Hz, 2H) 2.05 (s, 3H) 3.18 (s, 3H)3.47-3.55 (m, 2H) 3.67-3.76 (m, 2H) 4.77 (ddd, J=7.01, 3.44, 3.30 Hz,1H) 4.88-4.92 (m, 1H) 6.06 (s, 1H) 7.45 (s, 1H) 7.67 (d, J=8.80 Hz, 2H)8.10 (d, J=8.25 Hz, 2H). MS (ESI) 449.5.

Example 165 Preparation of6-methyl-1-(4-(methylsulfonyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 165 was prepared according to the procedure described in Example162, Step C, substituting 2-chloro-5-propylpyrimidine for2-chloro-5-cyclopropylpyrimidine. ¹H NMR (500 MHz, CDCl₃) δ ppm 8.16 (s,2H), 7.87 (dd, J=14.57, 7.97 Hz, 2H), 7.43-7.57 (m, 1H), 5.92 (d, J=9.90Hz, 2H), 4.48-4.59 (m, 1H), 4.18 (ddd, J=10.03, 7.01, 3.30 Hz, 2H),3.56-3.70 (m, 2H), 3.14 (s, 3H), 2.40 (t, J=7.42 Hz, 2H), 1.99-2.13 (m,2H), 1.94 (s, 3H), 1.83 (ddd, J=12.65, 8.25, 3.85 Hz, 2H), 1.46-1.66 (m,4H), 0.94 (t, 3H). MS (ESI) 501 (M+H).

Example 166 Preparation of(±)-4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-1-(2-fluoro-4-(methylsulfinyl)phenyl)pyridin-2(1H)-one

Example 166 was prepared according to procedures described in Example155 and 156 substituting in Example 155(4-bromo-3-fluorophenyl)(methyl)sulfane (Combi-Blocks) for(4-bromophenyl)(methyl)sulfane in Step C and substituting2-chloro-5-cyclopropylpyrimidine (prepared according to the proceduredescribed in Step A of Example 159) for 2-chloro-5-propylpyrimidine inStep E, except that the product of step C was purified by preparativeHPLC (C₁₈ column, 10-100% MeOH in water containing 0.1% trifluoroaceticacid). ¹H NMR (400 MHz, CDCl₃) δ ppm 8.11 (s, 2H), 7.44-7.63 (m, 3H),7.11 (d, J=7.82 Hz, 1H), 6.00-6.07 (m, 1H), 5.94-6.01 (m, 1H), 4.45-4.63(m, 1H), 4.09-4.25 (m, 2H), 3.55-3.67 (m, 2H), 2.77 (s, 3H), 1.97-2.14(m, 2H), 1.76-1.90 (m, 2H), 1.64-1.75 (m, 1H), 0.79-0.95 (m, 2 H),0.51-0.64 (m, 2H). MS (ESI) 469 (M+H).

Example 167 Preparation of(±)-1-(2-fluoro-4-(methylsulfinyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 167 was prepared according to procedures described in Example155 and 156 substituting in Example 155(4-bromo-3-fluorophenyl)(methyl)sulfane (Combi-Blocks) for(4-bromophenyl)(methyl)sulfane in Step C, except that the product ofstep C was purified by preparative HPLC (C₁₈ column, 10-100% MeOH inwater containing 0.1% trifluoroacetic acid). ¹H NMR (400 MHz, CDCl₃) δppm 8.18 (s, 2H), 7.48-7.66 (m, 3H), 7.14 (d, J=7.34 Hz, 1H), 6.06-6.09(m, 1H), 6.01-6.06 (m, 1H), 4.54-4.66 (m, 1H), 4.14-4.27 (m, 2H),3.59-3.72 (m, 2H), 2.80 (s, 3H), 2.42 (t, J=7.58 Hz, 2H), 2.02-2.16 (m,2H), 1.80-1.95 (m, 2H), 1.50-1.69 (m, 2H), 0.95 (t, J=7.34 Hz, 3H). MS(ESI) 471 (M+H).

Example 168 Preparation of tert-butyl4-(1-(2-chloro-4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 168 was prepared according to the procedures described inExample 1 substituting 2-chloro-1-fluoro-4-(methylsulfonyl)benzene for1-bromo-4-(methylsulfonyl)benzene in Step A and except that sodiumhydride was used instead of copper(I) iodide, 8-hydroxyquinoline andpotassium carbonate and the mixture was heated at 100° C. for 2 hinstead of heating in Microwave at 145° C. ¹H NMR (500 MHz, CDCl₃) δ ppm8.16 (s, 1H), 7.98 (dd, J=8.25, 2.20 Hz, 1H), 7.61 (d, J=8.25 Hz, 1H),7.05 (d, J=7.70 Hz, 1H), 6.08 (dd, J=7.70, 2.75 Hz, 1H), 5.99 (d, J=2.75Hz, 1H), 4.41-4.60 (m, 1H), 3.75 (d, J=4.95 Hz, 2H), 3.27-3.41 (m, 2H),3.14 (s, 3H), 1.95-2.05 (m, 2H), 1.80 (dd, J=7.70, 4.40 Hz, 2H),1.42-1.55 (m, 9H). MS (ESI) 483 (M+H).

Example 169 Preparation of1-(2-chloro-4-(methylsulfonyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 169 was prepared according to the procedures described inExample 168 and Example 162 substituting1-(2-chloro-4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloride for6-methyl-1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloride and 2-chloro-5-propylpyrimidine for2-chloro-5-cyclopropylpyrimidine in Step C. ¹H NMR (500 MHz, CDCl₃) δppm 8.19 (s, 2H), 8.16 (s, 1H), 7.99 (dd, J=8.25, 2.20 Hz, 1H), 7.62 (d,J=8.25 Hz, 1H), 7.06 (d, J=7.70 Hz, 1H), 6.10 (dd, J=7.70, 2.75 Hz, 1H),6.05 (d, J=2.75 Hz, 1H), 4.55-4.64 (m, 1H), 4.23 (dd, J=11.55, 6.05 Hz,2 H), 3.59-3.69 (m, 2H), 3.14 (s, 3H), 2.43 (t, J=7.42 Hz, 2H), 2.11(td, J=6.32, 3.30 Hz, 2H), 1.88 (ddd, J=8.39, 4.40, 4.26 Hz, 2H),1.55-1.61 (m, 2H), 0.96 (t, 3H). MS (ESI) 503 (M+H).

Example 170 Preparation of4-(1-(5-cyclopentenylpyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 170 was prepared according to procedures described in Example109 substituting cyclopentenylboronic acid (Combi-Blocks) forphenylboronic acid except that the reaction was heated under microwavecondition at 120° C. for 15 min and that the crude product was purifiedby flash chromatography (SiO₂, 0 to 100% EtOAc in CH₂Cl₂). ¹H NMR (400MHz, CDCl₃) δ ppm 8.40 (s, 2H), 8.04-8.11 (m, 2H), 7.57-7.67 (m, 2H),7.18-7.24 (m, 1H), 6.07-6.11 (m, 1H), 6.03-6.07 (m, 1 H), 6.01 (d,J=1.47 Hz, 1H), 4.50-4.65 (m, 1H), 4.16-4.26 (m, 2H) 3.64-3.77 (m, 2H)3.09 (s, 3H) 2.59-2.72 (m, 2H) 2.43-2.57 (m, 2H) 2.04-2.17 (m, 2H)1.94-2.04 (m, 2H) 1.78-1.92 (m, 2H). MS (ESI) 493 (M+H).

Example 171 Preparation of4-(1-(5-cyclopentylpyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 171 was prepared according to procedures described in Example120 Step C, substituting4-(1-(5-cyclopentenylpyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-onefor1-(4-(methylsulfonyl)phenyl)-4-(1-(5-(prop-1-en-2-yl)pyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-oneexcept that the reaction was stirred for 2 h and that the crude productwas purified by flash chromatography (SiO₂, 0 to 100% EtOAc in CH₂Cl₂).¹H NMR (400 MHz, CDCl₃) δ ppm 8.15 (s, 2H), 8.00 (d, J=8.80 Hz, 2H),7.56 (d, J=8.80 Hz, 2H), 7.16 (d, J=7.34 Hz, 1H), 6.00 (dd, J=7.34, 2.45Hz, 1H), 5.95 (d, J=2.45 Hz, 1H), 4.45-4.57 (m, 1 H), 4.06-4.19 (m, 2H),3.50-3.61 (m, 2H), 3.03 (s, 3H), 2.69-2.81 (m, 1H), 1.92-2.08 (m, 4H),1.68-1.85 (m, 4H), 1.56-1.69 (m, 2H), 1.36-1.46 (m, 2H). MS (ESI) 495(M+H).

Example 172 Preparation of1-(2-chloro-4-(methylsulfonyl)phenyl)-4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 172 was prepared according to the procedures described inExample 169 substituting 2-chloro-5-cyclopropylpyrimidine for2-chloro-5-propylpyrimidine. ¹H NMR (500 MHz, CDCl₃) δ ppm 8.14-8.15 (m,3H), 7.91-8.03 (m, 1H), 7.60 (d, J=8.25 Hz, 1H), 7.03 (d, J=7.70 Hz,1H), 6.07 (dd, J=7.42, 2.47 Hz, 1H), 6.01 (d, J=2.75 Hz, 1H), 4.58 (ddd,J=7.29, 3.85, 3.71 Hz, 1H), 4.12-4.24 (m, 1H), 3.67 (m, 2H), 3.10-3.18(m, 1H), 3.09 (s, 3H), 1.97-2.15 (m, 2H), 1.86 (d, J=3.85 Hz, 2H),1.65-1.77 (m, 1H), 0.85-1.00 (m, 2H), 0.48-0.66 (m, 2H). MS (ESI) 501(M+H).

Example 173 Preparation of1-(3-methyl-4-(methylsulfonyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Step A. Preparation of 1-(5-propylpyrimidin-2-yl)piperidin-4-ol

To a stirring solution of piperidin-4-ol (2.33 g, 23.0 mmol, Aldrich)and potassium carbonate (6.36 g, 46.0 mmol, EMD) in DMF (15 mL) at roomtemperature was added 2-chloro-5-propylpyrimidine (4.33 g, 27.6 mmol,Wako). The reaction mixture was heated at 100° C. for 3 h then dilutedwith H₂O. The resulting mixture was extracted with EtOAc (2×). Theorganic layers were combined, dried over Na₂SO₄ and concentrated invacuo to a brown oil. The oil was purified by flash chromatography(SiO₂, 0 to 100% EtOAc in CH₂Cl₂) to yield 5.01 g of desired product asa white solid. MS (ESI) 222 (M+H).

Step B. Preparation of 1-(5-propylpyrimidin-2-yl)piperidin-4-ylmethanesulfonate

To a stirring solution of 1-(5-propylpyrimidin-2-yl)piperidin-4-ol (9.2g, 41.6 mmol), Et₃N (12.85 mL, 91 mmol, Aldrich) in CH₂Cl₂ (80 mL) at 0°C. was added a solution of Methanesulfonyl chloride (3.54 mL, 45.7 mmol,Acros) in CH₂Cl₂ (20 mL) dropwise. The reaction mixture was stirred atroom temperature for 1 h and washed with 1N HCl in H₂O, saturated NaHCO₃in H₂O and brine. The organic layer was dried over Na₂SO₄ andconcentrated in vacuo to yield 11.7 g of the desired product as anoff-white solid. MS (ESI) 300 (M+H).

Step C. Preparation of4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

A stirring suspension of 4-hydroxypyridin-2(1H)-one (5.23 g, 47.1 mmol,Aldrich), 1-(5-propylpyrimidin-2-yl)piperidin-4-yl methanesulfonate(11.7 g, 39.2 mmol), potassium carbonate (12.5 g, 90.0 mmol, EMD) andDMSO (48 mL) was heated at 100° C. for 3 hours and then cooled to roomtemperature. The resulting mixture was diluted with H₂O and extractedwith EtOAc (2×). The organic layers were combined and concentrated invacuo to a brown solid. The solid was purified by flash chromatography(SiO₂, 100% EtOAc and then SiO₂, 10% MeOH in CH₂Cl₂) to yield 5.00 g ofdesired product as an off-white solid. MS (ESI) 315 (M+H).

Step D. Preparation of 4-bromo-2-methyl-1-(methylsulfonyl)benzene

A mixture of 4-bromo-1-iodo-2-methylbenzene (240 μL, 1.68 mmol,Aldrich), Copper(I) iodide (353 mg, 1.85 mmol, Alfa Aesar),Methanesulfinic acid, sodium salt (688 mg, 6.74 mmol, Alfa Aesar) andDMSO (7.2 mL) was purged with Argon and then heated under microwavecondition at 125° C. for 20 min. The resulting mixture was stirred at100° C. for 3 h and then cooled to room temperature. The reactionmixture was diluted with H₂O and extracted with EtOAc (2×). The organiclayers were combined and washed with brine, dried over Na₂SO₄ andconcentrated in vacuo to a white solid. The solid was purified by flashchromatography (SiO₂, 0-50% EtOAc in hexanes) to yield 270 mg of desiredproduct as a white solid. MS (ESI) 249 (M+H).

Step E Example 173

A mixture of 4-bromo-2-methyl-1-(methylsulfonyl)benzene (79 mg, 0.32mmol), 4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one(100 mg, 0.318 mmol), quinolin-8-ol (18.5 mg, 0.127 mmol, Alfa Aesar),potassium carbonate (57.1 mg, 0.414 mmol), Copper(I) iodide (24.2 mg,0.127 mmol, Alfa Aesar) in DMSO (4 mL) was stirred under Ar at 140° C.overnight. The resulting mixture was diluted with H₂O and extracted withEtOAc (2×). The combined organic layers were washed with brine, driedover Na₂SO₄ and concentrated in vacuo to a green oil. The oil waspurified by flash chromatography (SiO₂, 0 to 100% EtOAc in CH₂Cl₂) toyield 107.7 mg of desired product as a yellow solid. ¹H NMR (400 MHz,CDCl₃) δ ppm 8.10-8.22 (m, 3H), 7.34-7.43 (m, 2H), 7.18 (d, J=7.82 Hz,1H), 6.03 (dd, J=7.58, 2.20 Hz, 1H), 5.99 (d, J=2.45 Hz, 1H), 4.47-4.63(m, 1H), 4.13-4.22 (m, 2H), 3.56-3.69 (m, 2H), 3.09 (s, 3H), 2.73 (s,3H), 2.39 (t, J=7.58 Hz, 2H,) 2.00-2.12 (m, 2H), 1.75-1.92 (m, 2H),1.47-1.62 (m, 2H), 0.92 (t, J=7.34 Hz, 3H). MS (ESI) 483 (M+H).

Example 174 Preparation of1-(3-chloro-4-(methylsulfonyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 174 was prepared according to procedures described in Example173 substituting 4-bromo-2-chloro-1-iodobenzene (Alfa-Aesar) for4-bromo-1-iodo-2-methylbenzene in Step D. ¹H NMR (400 MHz, CDCl₃) δ ppm8.28 (d, J=8.31 Hz, 1H) 8.18 (s, 2H) 7.69 (d, J=1.47 Hz, 1H) 7.52 (dd,J=8.07, 1.71 Hz, 1H) 7.21 (d, J=7.82 Hz, 1H) 6.08 (dd, J=7.58, 2.20 Hz,1H) 6.01 (d, J=2.45 Hz, 1H) 4.52-4.63 (m, 1H) 4.13-4.27 (m, 2H)3.58-3.71 (m, 2H) 3.30 (s, 3H) 2.42 (t, J=7.34 Hz, 2 H) 2.04-2.16 (m,2H) 1.78-1.94 (m, 2H) 1.51-1.66 (m, 2H) 0.95 (t, J=7.34 Hz, 3 H). MS(ESI) 503 (M+H).

Example 175 Preparation of1-(3-fluoro-4-(methylsulfonyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 175 was prepared according to procedures described in Example173 substituting 4-bromo-2-fluoro-1-iodobenzene (Aldrich) for4-bromo-1-iodo-2-methylbenzene in Step D. ¹H NMR (400 MHz, CDCl₃) δ ppm8.15 (s, 2H), 8.06 (t, J=8.07 Hz, 1H), 7.42 (dd, J=10.27, 1.96 Hz, 1H),7.34 (dd, J=8.56, 1.71 Hz, 1H), 7.19 (d, J=7.34 Hz, 1H), 6.06 (dd,J=7.82, 2.45 Hz, 1H), 5.98 (d, J=2.45 Hz, 1H), 4.50-4.61 (m, 1H),4.12-4.25 (m, 2H), 3.53-3.70 (m, 2H), 3.23 (s, 3H), 2.39 (t, J=7.58 Hz,2H), 1.99-2.15 (m, 2H), 1.75-1.90 (m, 2H), 1.45-1.62 (m, 2H), 0.92 (t,J=7.34 Hz, 3H). MS (ESI) 487 (M+H).

Example 176 Preparation of tert-butyl4-(1-(4-cyano-2-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

To a mixture of tert-butyl4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (730 mg,2.480 mmol, Step A of Example 132) and DMF (12 mL) at room temperaturewas added sodium hydride (114 mg, 2.85 mmol). After stirring at roomtemperature for 1 hr, 3,4-difluorobenzonitrile (345 mg, 2.480 mmol,Aldrich) was added and the reaction mixture was heated at 100° C. for1.5 hrs and cooled to room temperature. The resulting mixture wasdiluted with EtOAc and water and the aqueous layer was extracted furtherwith EtOAc (3×). The combined organic extracts were washed with waterand brine, dried (MgSO₄) and evaporated under reduced pressure. Theresidue was purified by flash chromatography on silica gel (0-100% EtOAcin hexanes) to give the title compound (602.4 mg, 58.7%) as an off-whitesolid. ¹H NMR (500 MHz, CDCl₃) δ 7.47-7.64 (m, 3H), 7.10 (d, J=7.70 Hz,1H), 6.04 (dd, J=7.70, 2.20 Hz, 1H), 5.96 (d, J=2.20 Hz, 1H), 4.41-4.55(m, 1 H), 3.65-3.80 (m, 2H), 3.27-3.39 (m, 2H), 1.91-2.04 (m, 2H),1.71-1.84 (m, 2 H), 1.48 (s, 9H). MS (ESI) 358 (M+H—C₄H₈).

Example 177 Preparation of3-fluoro-4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)benzonitrile,TFA salt

Example 177 was prepared according to procedures described in Example132 substituting tert-butyl4-(1-(4-cyano-2-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(Example 176) for tert-butyl4-(2-oxo-1-(pyridin-3-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylateat Step C. ¹H NMR (500 MHz, CDCl₃) δ 8.17 (s, 2H), 7.49-7.64 (m, 3H),7.10 (d, J=7.70 Hz, 1H), 6.06 (dd, J=7.70, 2.75 Hz, 1H), 6.01 (d, J=2.20Hz, 1H), 4.53-4.62 (m, 1H), 4.15-4.25 (m, 2H), 3.56-3.70 (m, 2H), 2.41(t, J=7.70 Hz, 2H), 2.02-2.14 (m, 2 H), 1.76-1.92 (m, 2H), 1.51-1.65 (m,2H), 0.94 (t, J=7.15 Hz, 3H). MS (ESI) 434 (M+H).

Example 178 Preparation of1-(2-methyl-4-(methylsulfonyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 178 was prepared according to the procedures described inExample 162 substituting4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one forisopropyl 4-(methylsulfonyloxy)piperidine-1-carboxylate and1-fluoro-2-methyl-4-(methylsulfonyl)benzene for 4-bromobenzonitrile inStep C except that the reaction was heated at 160° C. for 20 min. withcopper(I) iodide, potassium carbonate and quinolin-8-ol in a Microwaveas described in Step A of Example 1 instead of reflux at 120° C. in thepresence of cesium carbonate for 10 h. ¹H NMR (500 MHz, CDCl₃) δ ppm8.21 (br. s., 2H), 7.92 (s, 1H), 7.88 (d, J=7.70 Hz, 1H), 7.40 (d,J=7.70 Hz, 1H), 7.06 (d, J=6.05 Hz, 1H), 5.93-6.11 (m, 2H), 4.58 (br.s., 1H), 4.21 (br. s., 2H), 3.56-3.80 (m, 2H), 3.08 (s, 3H), 2.41 (t,J=7.42 Hz, 2H), 2.28 (s, 3H), 2.09 (d, J=9.90 Hz, 2H), 1.87 (br. s.,2H), 1.48-1.65 (m, 2H), 0.93 (t, J=7.42 Hz, 3 H). MS (ESI) 483 (M+H).

Example 179 Preparation of3-fluoro-4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)benzamide,TFA salt

A mixture of3-fluoro-4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)benzonitrile(55.9 mg, 0.129 mmol, Example 177), acetamide (30.5 mg, 0.516 mmol,Aldrich) and zinc chloride (70.3 mg, 0.516 mmol, Alfa Aesar) in water(1.5 mL) and THF (1.5 mL) was heated under microwave conditions (155°C., 45 min). Additional acetamide (7.6 mg, 1 eq.) and zinc chloride(17.5 mg, 1.0 eq.) was added and the resulting mixture was heated againunder microwave conditions (155° C., 15 min). The reaction mixture wasdiluted with water and CH₂Cl₂ and aqueous layer was extracted furtherwith CH₂Cl₂ (2×). The combined extracts were washed with brine, dried(Na₂SO₄) and evaporated under reduced pressure. The residue was purifiedby preparative HPLC (C₁₈ column; 0-60% acetonitrile in water containing0.05% trifluoroacetic acid) to give Example 179 (36.1 mg, 62%) as alight yellow solid. ¹H NMR (400 MHz, CDCl₃) δ 8.33 (s, 2H), 7.70 (t,J=9.01 Hz, 2H), 7.43 (t, J=7.69 Hz, 1H), 7.18 (d, J=7.47 Hz, 1H), 6.68(brs, 1H), 6.06-6.17 (m, 2 H), 5.89 (brs, 1H), 4.59-4.72 (m, 1H),4.05-4.18 (m, 2H), 3.79-3.93 (m, 2H), 2.48 (t, J=7.69 Hz, 2H), 2.06-2.17(m, 2H), 1.90-2.03 (m, 2H), 1.55-1.67 (m, 2 H), 0.96 (t, J=7.25 Hz, 3H).MS (ESI) 452 (M+H).

Example 180 Preparation of1-(2-fluoro-4-(methylsulfonyl)phenyl)-5-phenyl-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Step A. Preparation of 6-chloro-4-hydroxy-5-phenylpyridin-2(1H)-one

To malonyl dichloride (17.43 mL, 179 mmol) under nitrogen in a 200 mLrecovery flask was added 2-phenylacetonitrile (9.80 mL, 85 mmol) and themixture was stirred under nitrogen at room temperature for 23 hours. Tothe resulting thick brown mixture was added ether (200 mL). Thisresulted in the formation of a brown, powder-like precipitate which wasfiltered at rt, washed with ether (4×50 mL), and then dried under vacuumto give crude product as a tan-amber powder (7.28 g). MS (ESI) 222(M+H).

Step B. Preparation of 4-hydroxy-5-phenylpyridin-2(1H)-one

A suspension of palladium on carbon (480 mg, 50 wt % wet, 0.451 mmol)and 6-chloro-4-hydroxy-5-phenylpyridin-2(1H)-one (1000 mg, 4.51 mmol) inEtOH (40 mL) was placed under a hydrogen balloon and stirred at 60° C.After stirring under hydrogen for 30 h, the mixture was filtered whilehot through a pad of CELITE® 545 filter aid and rinsed with hot ethanol.The filtrate was concentrated to give 490 mg crude product as a yellowsolid. MS (ESI) 188 (M+H).

Step C. Preparation of5-phenyl-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

The compound in Step C was prepared according to the proceduresdescribed in Example 1 substituting 4-hydroxy-5-phenylpyridin-2(1H)-onefor 4-hydroxy-1-(4-(methylsulfonyl)pyridine-2(1H)-one and1-(5-propylpyrimidin-2-yl)piperidin-4-yl methanesulfonate for tert-butyl4-(methylsulfonyloxy)piperidine-1-carboxylate in Step D. MS (ESI) 391(M+H).

Step D. Example 180

Example 180 was prepared according to the procedures described inExample 8 substituting5-phenyl-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-onefor isopropyl 4-(methylsulfonyloxy)piperidine-1-carboxylate and1,2-difluoro-4-(methylsulfonyl)benzene for 4-bromobenzonitrile in Step Cexcept that the Microwave reaction was run at 180° C. for 25 min. ¹H NMR(500 MHz, CDCl₃) δ ppm 8.16 (br. s., 2H), 7.82-7.93 (m, 2H), 7.64-7.74(m, 1 H), 7.30-7.46 (m, 5H), 7.19 (s, 1H), 6.12 (s, 1H), 4.71 (br. s.,1H), 3.85 (br. s., 4 H), 3.04-3.18 (m, 3H), 2.42 (t, J=7.47 Hz, 2H),1.82-2.11 (m, 4H), 1.49-1.65 (m, 2H), 0.93 (t, J=7.25 Hz, 3H). MS (ESI)563 (M+H).

Example 181 Preparation of1-(2-fluoro-4-(methylsulfonyl)phenyl)-4-(1-(5-(3,3,3-trifluoropropyl)pyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one,hydrochloride salt

Step A. Preparation of 2-chloro-5-(3,3,3-trifluoropropyl)pyrimidine

To magnesium (1.373 g, 56.5 mmol) in a 500 mL tear-shaped flask appliedvacuum then nitrogen, added 50 mL THF, added3-bromo-1,1,1-trifluoropropane (6.02 mL, 56.5 mmol), and then 1 crystalof iodine. Within 1 minute the mixture became warm and by 5 minutes wasrefluxing. The mixture was cooled for 2 minutes with an ice bath tocontrol the exothermic reaction then allowed to warm back up to rt. By65 minutes, nearly all of the Mg had dissolved. Added zinc(II) chloride(3.85 g, 28.3 mmol) which caused a small amount of heat to be generated.Nearly all was dissolved within 10 minutes to provide ˜1.1 M ofZn(CH₂CH₂CF₃)₂ in THF. To 5-bromo-2-chloropyrimidine (7.72 g, 39.9 mmol)and bis(tri-t-butylphosphine)palladium(0) (404 mg, 0.791 mmol) appliedvacuum then placed under an atmosphere of nitrogen, added 80 mL THF, andthen added over ˜2 minutes 60 mL of the ˜1.1 M of Zn(CH₂CH₂CF₃)₂ in THF.The reaction was quenched after 23 hour)s with 300 mL saturatedNH₄Cl+300 mL EtOAc, the organic layer was then washed with 300 mLsaturated NaHCO₃ then 300 mL water, dried with MgSO₄, filtered, thenconcentrated to 7.6 g brown oily solids. This material was purified byflash chromatography (0-10% EtOAc/hexanes) to yield product (3.86 g,18.4 mmol, 46% yield) as a pale yellow solid. MS (ESI) 211.1 (M+1).

Step B. Preparation of1-(5-(3,3,3-trifluoropropyl)pyrimidin-2-yl)piperidin-4-ylmethanesulfonate

In a manner similar to that described in Example 142, Steps A and B,2-chloro-5-(3,3,3-trifluoropropyl)pyrimidine (Example 181, Step A) wasconverted into 1-(5-(3,3,3-trifluoropropyl)pyrimidin-2-yl)piperidin-4-ylmethanesulfonate.

Step C. Preparation of Example 181

To 1-(2-fluoro-4-(methylsulfonyl)phenyl)-4-hydroxypyridin-2(1H)-one (85mg, 0.3 mmol), obtained as described in Example 142, Step D, was added1-(5-(3,3,3-trifluoropropyl)pyrimidin-2-yl)piperidin-4-ylmethanesulfonate (106 mg, 0.300 mmol), potassium carbonate (54.0 mg,0.900 mmol), and then 1 mL DMF, the mixture placed in a 90° C. oil bathfor 345 minutes. To this was added 5 mL EtOAc and the mixture washedwith 2×2 mL water, dried with MgSO₄, filtered and concentrated to 99 mg(0.183 mmol) of yellow solids to which were added 2 mL EtOH and then 125uL of 6 N aqueous HCl (0.75 mmol, 4.1 equiv.). All dissolved withstirring within one minute. Stirred for an additional 5 minutes thesolvent was removed in vacuo to yield 110 mg of a pale yellow solid towhich were added 3 mL EtOH and the mixture heated to reflux at whichpoint the solids appeared to become white to tan and crystalline. Cooledto rt, filtered and washed with 2×0.5 mL EtOH, then dried in vacuo toyield Example 181 (33 mg, 0.057 mmol, 19%) as an off-white, crystallinepowder. ¹H NMR (500 MHz, methanol-d₃) δ ppm 2.01 (m, 2H) 2.13-2.31 (m,2H) 2.43-2.70 (m, 2H) 2.79-3.01 (m, 2H) 3.22 (s, 3H) 3.86-4.03 (m, 2 H)4.05-4.30 (m, 2H) 6.13 (d, J=2.75 Hz, 1H) 6.31 (dd, J=7.70, 2.20 Hz, 1H)7.57 (d, J=7.15 Hz, 1H) 7.67-7.82 (m, 1H) 7.87-8.07 (m, 2H) 8.58 (s,2H). MS (ESI) 541.1.

Example 182 Preparation of1-(4-(methylsulfonyl)-3-(trifluoromethyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 182 was prepared according to procedures described in Example173 substituting 4-bromo-1-iodo-2-(trifluoromethyl)benzene (Oakwood) for4-bromo-1-iodo-2-methylbenzene in Step D. ¹H NMR (500 MHz, CDCl₃) δ ppm8.43 (d, J=8.80 Hz, 1H), 8.16 (s, 2H), 7.95 (d, J=2.20 Hz, 1H), 7.85(dd, J=8.25, 2.20 Hz, 1H), 7.23 (d, J=7.70 Hz, 1H), 6.11 (dd, J=7.70,2.20 Hz, 1H), 6.01 (d, J=2.75 Hz, 1 H), 4.51-4.63 (m, 1H), 4.14-4.24 (m,2H), 3.60-3.69 (m, 2H), 3.21 (s, 3H), 2.40 (t, J=7.70 Hz, 2H), 2.04-2.12(m, 2H), 1.79-1.90 (m, 2H), 1.52-1.64 (m, 2H), 0.94 (t, J=7.15 Hz, 3H).MS (ESI) 537 (M+H).

Example 183 Preparation of5-cyclopropyl-1-(2-fluoro-4-(methylsulfonyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one,TFA salt

Example 183 was prepared according to the procedures described inExample 180 substituting 2-cyclopropylacetonitrile for2-phenylacetonitrile in Step A. ¹H NMR (500 MHz, CDCl₃) δ ppm 8.34-8.50(m, 2H), 7.77-7.95 (m, 2H), 7.60 (t, J=7.69 Hz, 1H), 6.95 (s, 1H), 6.45(s, 1H), 4.84 (br. s., 1H), 4.24-4.39 (m, 2H), 3.89-4.06 (m, 2H), 3.12(s, 3H), 2.55 (t, J=7.47 Hz, 2H), 2.17 (d, 4H), 1.71-1.80 (m, 1H),1.55-1.70 (m, 2H), 0.91-1.05 (m, 3H), 0.81-0.92 (m, 2H), 0.40-0.54 (m,2H). MS (ESI) 527 (M+H).

Example 185 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-phenylpiperidin-4-yloxy)pyridin-2(1H)-one,TFA salt

To 1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-one,HCl salt (35 mg, 0.100 mmol), phenylboronic acid (24.50 mg, 0.201 mmol),copper (II) acetate (27.4 mg, 0.151 mmol), and 75 mg of 4 A molecularsieves (oven dried) was added 1.5 mL of CH₂Cl₂, and then pyridine (0.016mL, 0.201 mmol. The tan suspension was stirred open to air for 2-3minutes then capped with continued stirring. The mixture developed apale green-blue tint within 3-4 minutes. After 89 hours, added 4 mLCH₂Cl₂ then washed with 3×3 mL saturated aqueous NH₄Cl, dried organiclayer with MgSO₄, filtered, then concentrated to provide 14 mg palegrey-green solids which was purified by preparative HPLC (C₁₈ column;MeOH in water containing 0.1% TFA) to yield Example 185 (1.27 mg, 0.001mmol, 1%) as a pale yellow oil. MS (ESI) 425.1 (M+1). ¹H NMR (500 MHz,methanol-d₃) δ ppm 2.05-2.18 (m, 2H) 2.23-2.38 (m, 2H) 3.17 (s, 3H) 3.44(s, 1H) 3.57-3.74 (m, 1 H) 6.11 (d, J=2.75 Hz, 1H) 6.31 (dd, J=7.70,2.75 Hz, 1H) 7.16 (br. s., 1H) 7.31 (d, J=7.70 Hz, 1H) 7.41 (t, J=7.70Hz, 1H) 7.61 (d, J=7.70 Hz, 1H) 7.64-7.73 (m, 2 H) 8.11 (d, 2H). MS(ESI) 425.1 (M+1).

Example 186 Preparation of1-(2-methylpyridin-3-yl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 186 was prepared according to procedures described in Example173 substituting 3-bromo-2-methylpyridine (3B Pharmachem) for4-bromo-2-methyl-1-(methylsulfonyl)benzene in Step E except that crudesolid was purified by flash chromatography (SiO₂, 0 to 10% MeOH inCH₂Cl₂) and by preparative HPLC (C₁₈ column, 10-100% MeOH in watercontaining 0.1% trifluoroacetic acid). ¹H NMR (500 MHz, CDCl₃) δ ppm8.52 (d, J=3.85 Hz, 1H), 8.10 (s, 2H), 7.47 (dd, J=8.25, 1.10 Hz, 1H),7.20-7.23 (m, 1H), 6.98 (d, J=7.70 Hz, 1H), 5.97-5.99 (m, 1H), 5.96 (s,1H), 4.48-4.53 (m, 1H), 4.12-4.18 (m, 2H), 3.53-3.58 (m, 2H), 2.37 (s,3H), 2.34 (t, J=7.70 Hz, 2H), 2.00-2.05 (m, 2H), 1.75-1.82 (m, 2H),1.47-1.55 (m, 2H), 0.87 (t, J=7.42 Hz, 3H). MS (ESI) 406 (M+H).

Example 187 Preparation of1-(6-(methylsulfonyl)pyridin-3-yl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 187 was prepared according to procedures described in Example173 substituting 5-bromo-2-(methylsulfonyl)pyridine (Synthonix) for4-bromo-2-methyl-1-(methylsulfonyl)benzene in Step E except thatreaction was heated under microwave condition at 160° C. for 30 min. ¹HNMR (400 MHz, CDCl₃) δ ppm 8.79 (d, J=2.20 Hz, 1H) 8.23 (d, J=8.24 Hz,1H) 8.17 (s, 2H) 8.07 (dd, J=8.25, 2.20 Hz, 1H) 7.23 (d, J=7.70 Hz, 1H)6.12 (dd, J=7.70, 2.20 Hz, 1H) 6.02 (d, J=2.20 Hz, 1 H) 4.55-4.62 (m,1H) 4.16-4.24 (m, 2H) 3.60-3.68 (m, 2H) 3.27 (s, 3H) 2.41 (t, 2H)2.05-2.13 (m, 2H) 1.80-1.90 (m, 2H) 1.53-1.63 (m, 2H) 0.94 (t, J=7.42Hz, 3H). MS (ESI) 470 (M+H).

Example 188 Preparation of isopropyl4-(1-(4-cyano-2-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 188 was prepared according to procedures described in Example132 substituting tert-butyl4-(1-(4-cyano-2-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(Example 176) for tert-butyl4-(2-oxo-1-(pyridin-3-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatein Step C and substituting isopropyl carbonochloridate (1 Molar inToluene, Aldrich) for 2-chloro-5-propylpyrimidine and substitutingtriethyl amine for cesium carbonate in Step D except that reaction wasstirred at room temperature for 20 min and then washed with HCl solution(1 Molar in H₂O). The crude solid was purified by flash chromatography(SiO₂, 0 to 100% EtOAc in CH₂Cl₂). ¹H NMR (500 MHz, CDCl₃) δ ppm7.49-7.58 (m, 3H), 7.08 (d, J=7.70 Hz, 1H), 6.02 (dd, J=7.70, 2.20 Hz,1H), 5.93 (d, J=2.20 Hz, 1H), 4.87-4.95 (m, 1H), 4.45-4.49 (m, 1H),3.69-3.77 (m, 2H), 3.32-3.39 (m, 2H), 1.92-2.00 (m, 2H), 1.72-1.81 (m,2H), 1.24 (d, J=6.60 Hz, 6H). MS (ESI) 400 (M+H).

Example 189 Preparation of isopropyl4-(1-(6-(methylsulfonyl)pyridin-3-yl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Step A. Preparation of isopropyl 4-hydroxypiperidine-1-carboxylate

To a stirring solution of piperidin-4-ol (5.22 g, 51.6 mmol, Aldrich),Et₃N (13.2 mL, 95 mmol, Aldrich) in CH₂Cl₂ (50 mL) at 0° C. was added asolution of Isopropyl chloroformate (1 Molar in Toluene, 43.0 mL, 43.0mmol, Aldrich) dropwise. The reaction mixture was stirred at roomtemperature for 1 h and washed with 1N HCl in H₂O. The H₂O layer wasextracted with DCM (2×). The organic layers were combined andconcentrated in vacuo to yield 5.71 g of the desired product as a lightbrown oil. MS (ESI) 188 (M+H).

Step B Example 189

Example 189 was prepared according to procedures described in Example173 substituting isopropyl 4-hydroxypiperidine-1-carboxylate for1-(5-propylpyrimidin-2-yl)piperidin-4-ol in Step B and substituting5-bromo-2-(methylsulfonyl)pyridine for4-bromo-2-methyl-1-(methylsulfonyl)benzene in Step E except thatreaction was heated under microwave condition at 160° C. for 30 min. ¹HNMR (500 MHz, CDCl₃) δ ppm 8.78 (d, J=2.20 Hz, 1H), 8.22 (d, J=8.25 Hz,1H), 8.06 (dd, J=8.25, 2.75 Hz, 1H), 7.23 (d, J=7.70 Hz, 1H), 6.11 (dd,J=7.70, 2.20 Hz, 1H), 5.98 (d, J=2.75 Hz, 1H), 4.90-4.98 (m, 1H),4.49-4.54 (m, 1H), 3.72-3.79 (m, 2H), 3.36-3.42 (m, 2H), 3.27 (s, 3H),1.96-2.03 (m, 2H), 1.76-1.84 (m, 2 H), 1.26 (d, J=6.05 Hz, 6H). MS (ESI)436 (M+H).

Example 190 Preparation of4-(4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-2-oxopyridin-1(2H)-yl)-3-fluorobenzonitrile

Example 190 was prepared according to procedures described in Example132 substituting tert-butyl4-(1-(4-cyano-2-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(Example 176) for tert-butyl4-(2-oxo-1-(pyridin-3-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatein Step C and substituting 2-chloro-5-cyclopropylpyrimidine (preparedaccording to the procedure described in Step A of Example 159) for2-chloro-5-propylpyrimidine and substituting potassium carbonate forcesium carbonate in Step D except that reaction was stirred at 100° C.for 7 h. The crude solid was purified by flash chromatography (SiO₂, 0to 100% EtOAc in CH₂Cl₂). ¹H NMR (500 MHz, CDCl₃) δ ppm 8.14 (s, 2H),7.51-7.62 (m, 3H), 7.11 (d, J=7.70 Hz, 1H), 6.06 (dd, J=7.70, 2.75 Hz,1H), 6.01 (d, J=2.75 Hz, 1H), 4.52-4.62 (m, 1H), 4.15-4.26 (m, 2H),3.58-3.68 (m, 2H), 1.96-2.14 (m, 2 H), 1.79-1.96 (m, 2H), 1.69-1.77 (m,1H), 0.88-0.96 (m, 2H), 0.57-0.64 (m, 2 H). MS (ESI) 432 (M+H).

Example 191 Preparation of isopropyl4-(2-oxo-1-(pyrimidin-5-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 191 was prepared according to procedures described in Example189 substituting 5-bromopyrimidine (Aldrich) for5-bromo-2-(methylsulfonyl)pyridine in Step B. ¹H NMR (400 MHz, CDCl₃) δppm 9.28 (br. s., 1 H), 8.91 (br. s., 2H), 7.23 (d, J=7.53 Hz, 1H), 6.11(dd, J=7.65, 2.64 Hz, 1H), 5.99 (d, J=2.76 Hz, 1H), 4.91-5.01 (m, 1H),4.50-4.56 (m, 1H), 3.72-3.82 (m, 2H), 3.34-3.46 (m, 2H), 1.96-2.05 (m,2H), 1.75-1.86 (m, 2H), 1.28 (d, J=6.27 Hz, 6 H). MS (ESI) 359 (M+H).

Example 192 Preparation of4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)-1-(pyrimidin-5-yl)pyridin-2(1H)-one

Example 192 was prepared according to procedures described in Example187 substituting 5-bromopyrimidine (Aldrich) for5-bromo-2-(methylsulfonyl)pyridine. ¹H NMR (400 MHz, CDCl₃) δ ppm 9.27(br. s., 1H), 8.91 (br. s., 2H), 8.19 (s, 2H), 7.23 (d, J=7.78 Hz, 1H),6.12 (dd, J=7.65, 2.64 Hz, 1H), 6.04 (d, J=2.76 Hz, 1H), 4.57-4.64 (m,1H), 4.18-4.25 (m, 2H), 3.62-3.71 (m, 2 H), 2.43 (t, J=7.53 Hz, 2H),2.06-2.15 (m, 2H), 1.82-1.92 (m, 2H), 1.57-1.65 (m, 2H), 0.96 (t, J=7.28Hz, 3H). MS (ESI) 393 (M+H).

Example 193 Preparation of4-(1-(5-sec-butylpyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one,hydrochloride salt

To Example 57 (51 mg, 0.101 mmol) and bis(tri-t-butylphosphine)palladium(4 mg, 0.020 mmol) was added 0.5 mL THF under nitrogen giving a pale tansuspension. Added at rt 0.605 mL of sec-butylzinc(II) bromide (0.605 mL,0.303 mmol, 0.5 M in THF) and stirred for 19.5 hours at which point thereaction was quenched with 2 mL EtOAc then washed with 1 mL each ofsaturated aqueous NH₄Cl, NaHCO₃, then NaCl. Dried with MgSO₄, filteredand then concentrated to 43 mg brown solids. Added ˜1 mL of 90% MeOH/10%water/0.1% TFA which did not dissolve the solids. Purified this materialon a 500 uM silica TLC plate developed with 5% MeOH/CHCl₃ to provide 28mg (0.058 mmol) of an off-white powder. This material was suspended in0.5 mL EtOH and to which was then added 40 uL of 6N aqueous HCl (0.240mmol, 4.1 equiv) causing complete dissolution. Within 2 minutes,crystals began to form. Filtered after 30 minutes plus 2×0.3 mL EtOHwash to give Example 193 (18 mg, 0.034 mmol, 33%) as pale tan crystals.¹H NMR (400 MHz, CDCl₃) δ ppm 1.04 (t, J=7.25 Hz, 3H) 1.43 (d, J=7.03Hz, 3H) 1.67-1.87 (m, 2H) 2.15-2.36 (m, 4H) 2.77-2.89 (m, 1H) 3.28 (br.s., 3H) 4.10-4.27 (m, 3H) 4.94 (br. s., 1H) 6.19 (s, 1H) 6.28-6.39 (m,1H) 7.45-7.54 (m, 3H) 7.47-7.53 (m, 2H) 7.77 (d, J=8.35 Hz, 2H) 8.23 (d,J=8.35 Hz, 2H) 8.57 (br. s., 2H). MS (ESI) 483.1 (M+1).

Example 194 Preparation of5-chloro-1-(4-(methylsulfonyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one,TFA salt

Step A. Preparation of 1-(5-propylpyrimidin-2-yl)piperidin-4-ol

A suspension of piperidin-4-ol (12 g, 119 mmol),2-chloro-5-propylpyrimidine (20.44 g, 131 mmol) and potassium carbonate(49.2 g, 356 mmol) in DMF (100 mL) was heated at 110° C. for 12 h andcooled to rt. The mixture was diluted with EtOAc (250 ml) and washedwith H₂O (3×). After drying over Na₂SO₄, the organic layer wasevaporated to give a yellow oil. The crude oil was purified on a flashchromatography (SiO₂, 0 to 10% MeOH/CH₂Cl₂) to give a yellow solid. MS(ESI) 222 (M+H).

Step B. Preparation of 1-(5-propylpyrimidin-2-yl)piperidin-4-ylmethanesulfonate

The compound was prepared according to the procedures described inExample 1 substituting 1-(5-propylpyrimidin-2-yl)piperidin-4-ol fortert-butyl 4-hydroxypiperidine-1-carboxylate in Step C. MS (ESI) 300(M+H).

Step C. Preparation of5-chloro-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

A mixture of 1-(5-propylpyrimidin-2-yl)piperidin-4-yl methanesulfonate(800 mg, 2.67 mmol), 5-chloro-4-hydroxypyridin-2(1H)-one (389 mg, 2.67mmol, AK Scientific) and cesium carbonate (2612 mg, 8.02 mmol) in DMF(20 mL) was heated at 120° C. for 6 h. The reaction was cooled to rt,diluted with EtOAc (30 mL), and washed with H₂O (3×). The organic layerwas dried over Na₂SO₄ and concentrated under reduced pressure to give ayellow solid. The residue was purified by flash chromatography (SiO₂,O-10% MeOH/CH₂Cl₂) to give the desired product as a yellow solid. MS(ESI) 379 (M+H).

Step 4 Example 194

Example 194 was prepared according to the procedures described inExample 8 substituting5-chloro-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-onefor isopropyl 4-(methylsulfonyloxy)piperidine-1-carboxylate andsubstituting 1-bromo-4-(methylsulfonyl)benzene for 4-bromobenzonitrilein Step C in addition to running the Microwave reaction at 190° C. for25 min. ¹H NMR (500 MHz, CDCl₃) δ ppm 8.43 (s, 2H), 8.12 (d, J=8.25 Hz,2H), 7.62 (d, J=8.25 Hz, 2H), 7.55 (s, 1H), 6.64 (s, 1H), 4.89 (br. s.,1H), 4.24-4.37 (m, 2H), 3.90-4.07 (m, 2H), 3.12 (s, 3H), 2.56 (t, J=7.70Hz, 2H), 2.19 (br. s., 4H), 1.57-1.75 (m, 2H), 0.84-1.10 (m, 3H). MS(ESI) 503 (M+H).

Example 195 Preparation of4-(2-(4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidin-1-yl)pyrimidin-5-yl)benzonitrile,hydrochloride salt

To a suspension of4-(1-(5-bromopyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one(51 mg, 0.101 mmol) and bis(tri-t-butylphosphine)palladium (4.08 mg,0.020 mmol) in 0.5 mL of THF under nitrogen at rt was added 0.605 mL of0.5 M (4-cyanophenyl)zinc(II) bromide (74.9 mg, 0.303 mmol) in THF. Thereaction was quenched after 25 minutes with 2 mL of saturated aqueousNaHCO₃+4 mL EtOAc, then removed EtOAc and washed with an additional 2 mLof saturated aqueous NaHCO₃, then 2 mL of brine. The poorly solubleproduct had precipitated out during this process and remained in a thinemulsion-like layer at the interface of the aqueous and organic phases.Upon carefully isolating this layer it was filtered and the solidswashed with EtOAc (mL) to produce 17 mg of a pale yellow solid. Thismaterial was suspended in 3 mL EtOH to which were added 100 uL 6 Naqueous HCl (0.6 mmol, 9.5 equiv) and the mixture heated to refluxcausing nearly complete solution and then allowed cool to rt. Smallcrystals formed slowly. Filtered plus 0.5 mL EtOH then 2×0.5 mL hexanewashes to yield Example 195 (11 mg) as bright yellow crystals. ¹H NMR(500 MHz, DMSO-d₆) δ ppm 1.54-1.76 (m, 2H) 2.07 (d, J=8.80 Hz, 2H)3.35-3.55 (m, 5H) 3.62 (t, J=10.17 Hz, 2H) 4.31 (d, J=13.75 Hz, 2H) 4.82(d, J=3.85 Hz, 1H) 6.08-6.15 (m, 2 H) 7.66 (d, J=7.70 Hz, 1H) 7.70 (d,J=8.80 Hz, 2H) 7.83-7.96 (m, 4H) 8.04 (d, J=8.25 Hz, 2H) 8.84 (s, 2H).MS (ESI) 528.1 (M+1).

Example 196 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(4-propylphenyl)piperidin-4-yloxy)pyridin-2(1H)-one,TFA salt

To a mixture of1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-onehydrochloride (50 mg, 0.130 mmol, prepared according to the proceduresdescribed in Example 1), 4-propylphenylboronic acid (42.6 mg, 0.260mmol) and diacetoxycopper (35.4 mg, 0.195 mmol) in CH₂Cl₂ (3 mL) wasadded pyridine (0.021 mL, 0.260 mmol). After exposure to open air for5-10 min., the reaction mixture was capped and stirred with 4 A°molecular sieves at rt for 48 h. To the reaction mixture was dilutedwith CH₂Cl₂ and washed with saturated aq. NH₄Cl (3×). The organic layerwas dried (Na₂SO₄) and evaporated under reduced pressure. The residuewas purified by preparative HPLC (C₁₈ column; 20-90% MeOH in watercontaining 0.1% trifluoroacetic acid) to give Example 196 (6 mg, 9.90%)as a white solid. ¹H NMR (500 MHz, CDCl₃) δ ppm 8.10 (d, J=7.70 Hz, 2H),7.53-7.72 (m, 4H), 7.33 (d, J=7.70 Hz, 3H), 6.34-6.53 (m, 1H), 6.18-6.34(m, 1H), 4.72-4.87 (m, 1H), 3.73 (d, J=7.15 Hz, 2H), 3.62 (br. s., 2H),3.11 (s, 3H), 2.84 (d, J=4.40 Hz, 2H), 2.63 (t, J=7.42 Hz, 2H),2.38-2.53 (m, 2H), 1.55-1.73 (m, 2H), 0.95 (t, J=7.15 Hz, 3H). MS (ESI)466 (M+H).

Example 197 Preparation of isopropyl4-(1-(4-cyano-3-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 197 was prepared according to procedures described in Example189 substituting 4-bromo-2-fluorobenzonitrile (Lancaster) for5-bromo-2-(methylsulfonyl)pyridine in Step B. ¹H NMR (400 MHz, CDCl₃) δ7.76 (dd, J=8.03, 7.03 Hz, 1H), 7.32-7.43 (m, 2H), 7.22 (d, J=7.78 Hz,1H), 6.07 (dd, J=7.78, 2.51 Hz, 1H), 5.96 (d, J=2.51 Hz, 1H), 4.91-5.00(m, 1H), 4.48-4.55 (m, 1H), 3.72-3.82 (m, 2H), 3.36-3.44 (m, 2H),1.96-2.05 (m, 2H), 1.75-1.85 (m, 2H), 1.28 (d, J=6.27 Hz, 6H). MS (ESI)400 (M+H).

Example 198 Preparation of4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)-1-(pyrazin-2-yl)pyridin-2(1H)-one

Example 198 was prepared according to procedures described in Example187 substituting 2-iodopyrazine (Aldrich) for5-bromo-2-(methylsulfonyl)pyridine except that the reaction was heatedunder microwave conditions at 140° C. for 20 min. ¹H NMR (400 MHz,CDCl₃) δ ppm 9.40 (s, 1H), 8.58 (d, J=2.51 Hz, 1H), 8.50-8.55 (m, 1H),8.19 (s, 2H), 7.85 (d, J=7.78 Hz, 1H), 6.12 (dd, J=7.91, 2.64 Hz, 1H),6.02 (d, J=2.26 Hz, 1H), 4.58-4.65 (m, 1H), 4.17-4.25 (m, 2H), 3.63-3.71(m, 2 H), 2.40-2.46 (m, 2H), 2.07-2.14 (m, 2H), 1.82-1.92 (m, 2H),1.55-1.64 (m, 2 H), 0.96 (t, J=7.40 Hz, 3H). MS (ESI) 393 (M+H).

Example 199 Preparation of2-fluoro-4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)benzonitrile

Example 199 was prepared according to procedures described in Example187 substituting 2-fluoro-4-iodobenzonitrile (Matrix Scientific) for5-bromo-2-(methylsulfonyl)pyridine except that the reaction was heatedunder microwave conditions at 125° C. for 1 h. ¹H NMR (400 MHz, CDCl₃) δppm 8.18 (s, 2H), 7.76 (dd, J=8.28, 7.03 Hz, 1H), 7.31-7.44 (m, 2H),7.21 (d, J=7.78 Hz, 1H), 6.08 (dd, J=7.78, 2.51 Hz, 1H), 6.00 (d, J=2.51Hz, 1H), 4.51-4.63 (m, 1H), 4.14-4.27 (m, 2H), 3.58-3.70 (m, 2H), 2.42(t, J=7.53 Hz, 2H), 1.97-2.16 (m, 2H), 1.79-1.97 (m, 2H), 1.53-1.65 (m,2H), 0.95 (t, J=7.40 Hz, 3H). MS (ESI) 434 (M+H).

Example 200 Preparation of isopropyl4-(2-oxo-1-(pyrazin-2-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 200 was prepared according to procedures described in Example189 substituting 2-iodopyrazine (Aldrich) for5-bromo-2-(methylsulfonyl)pyridine in Step B. ¹H NMR (400 MHz, CDCl₃) δppm 9.37 (d, J=1.51 Hz, 1H), 8.57 (d, J=2.51 Hz, 1H), 8.50-8.54 (m, 1H),7.85 (d, J=8.03 Hz, 1H), 6.11 (dd, J=7.91, 2.64 Hz, 1 H), 5.95 (d,J=2.51 Hz, 1H), 4.91-5.00 (m, 1H), 4.50-4.57 (m, 1H), 3.71-3.81 (m, 2H),3.37-3.47 (m, 2H), 1.96-2.06 (m, 2H), 1.77-1.87 (m, 2H), 1.28 (d, J=6.27Hz, 6H). MS (ESI) 359 (M+H).

Example 201 Preparation of5-chloro-4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one,TFA salt

Example 201 was prepared according to the procedures described inExample 194 substituting 2-chloro-5-cyclopropylpyrimidine for2-chloro-5-propylpyrimidine in Step A. ¹H NMR (500 MHz, CDCl₃) δ ppm8.37 (s, 2H), 8.11 (d, J=8.25 Hz, 2H), 7.62 (d, J=8.80 Hz, 2H), 7.53 (s,1H), 6.55 (br. s., 1H), 4.78-4.93 (m, 1H), 4.26 (br. s., 2H), 3.96 (br.s., 2H), 3.12 (s, 3H), 2.16 (br. s., 4H), 1.83 (br. s., 1H), 1.71-1.92(m, 1H), 1.10 (d, J=8.25 Hz, 2H), 0.74 (d, J=5.50 Hz, 2H). MS (ESI) 501(M+H).

Example 203 Preparation of1-(4-aminophenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 203 was prepared according to procedures described in Example173 substituting tert-butyl 4-iodophenylcarbamate (Oakwood) for4-bromo-2-methyl-1-(methylsulfonyl)benzene in Step E except thatreaction was heated at 100° C. overnight and then heated at 140° C. for3 h. The crude solid was purified by flash chromatography (SiO₂, 0 to10% MeOH in CH₂Cl₂). ¹H NMR (400 MHz, CDCl₃) δ ppm 8.18 (s, 2H), 7.22(d, J=7.53 Hz, 1H), 7.11-7.16 (m, 2H), 6.72-6.78 (m, 2H), 6.02 (d,J=2.76 Hz, 1H), 5.96 (dd, J=7.53, 2.76 Hz, 1H), 4.52-4.59 (m, 1H),4.17-4.25 (m, 2H), 3.81 (s, 2H), 3.58-3.67 (m, 2H), 2.39-2.45 (m, 2H),2.05-2.13 (m, 2H), 1.79-1.89 (m, 2H), 1.54-1.64 (m, 2H), 0.96 (t, J=7.40Hz, 3H). MS (ESI) 406 (M+H).

Example 205 Preparation of1-(4-(2-oxopyrrolidin-1-yl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one,hydrochloride salt

Example 205 was prepared according to procedures described in Example187 substituting 1-(4-bromophenyl)pyrrolidin-2-one (Oakwood) for5-bromo-2-(methylsulfonyl)pyridine except that the crude solid waspurified by flash chromatography (SiO₂, 0 to 100% EtOAc in hexanes) andthen converted to the hydrochloride salt by addition of 1 equivalent ofHCl (1N HCl in Et₂O) to the compound stirring in CH₂Cl₂ for 5 minfollowed by concentration in vacuo to the desired product. ¹H NMR (400MHz, CDCl₃) δ ppm 8.43 (br. s., 2H), 7.77 (d, J=8.53 Hz, 2H), 7.39 (d,J=8.53 Hz, 2H), 7.29-7.33 (m, 1H), 6.12 (br. s., 1H), 6.06 (d, J=7.53Hz, 1H), 4.68-4.77 (m, 1H), 4.27-4.38 (m, 2H), 4.07-4.19 (m, 2H), 3.92(t, J=7.03 Hz, 2H), 2.66 (t, J=8.16 Hz, 2H), 2.55 (t, J=7.53 Hz, 2H),2.16-2.26 (m, 2H), 2.10-2.16 (m, 4H), 1.61-1.71 (m, 2H), 1.00 (t, J=7.28Hz, 3H). MS (ESI) 474 (M+H).

Example 206 Preparation of1-(2-methyl-6-(methylsulfonyl)pyridin-3-yl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one,TFA salt

Example 206 was prepared according to procedures described in Example173 substituting 3,6-dibromo-2-methylpyridine (Synchem) for4-bromo-1-iodo-2-methylbenzene in Step D and the final product waspurified by preparative HPLC (C₁₈ column, 10-100% MeOH in watercontaining 0.1% trifluoroacetic acid). ¹H NMR (400 MHz, CDCl₃) δ ppm8.44 (s, 2H), 8.11 (d, J=8.03 Hz, 1H), 7.81 (d, J=8.28 Hz, 1H), 7.13 (d,J=7.78 Hz, 1H), 6.31 (d, J=2.26 Hz, 1H), 6.24 (dd, J=7.65, 2.38 Hz, 1H),4.71-4.79 (m, 1H), 4.03-4.10 (m, 4H), 3.31 (s, 3H), 2.52-2.57 (m, 5H),2.13-2.21 (m, 2H), 2.04-2.12 (m, 2H), 1.61-1.71 (m, 2H), 1.00 (t, J=7.28Hz, 3H). MS (ESI) 484 (M+H).

Example 207 Preparation of isopropyl4-(1-(2-methyl-6-(methylsulfonyl)pyridin-3-yl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate,TFA salt

Example 207 was prepared according to procedures described in Example189 substituting 3-bromo-2-methyl-6-(methylsulfonyl)pyridine (preparedaccording to the procedure described in Step D of Example 173substituting 3,6-dibromo-2-methylpyridine for4-bromo-1-iodo-2-methylbenzene) for 5-bromo-2-(methylsulfonyl)pyridinein Step B except that reaction was heated at 140° C. overnight and thatthe crude product was purified by preparative HPLC (C₁₈ column, 10-100%MeOH in water containing 0.1% trifluoroacetic acid). ¹H NMR (400 MHz,CDCl₃) δ ppm 8.07 (d, J=8.03 Hz, 1H), 7.78 (d, J=8.03 Hz, 1H), 7.10 (d,J=7.78 Hz, 1H), 6.33 (d, J=2.26 Hz, 1H), 6.23 (dd, J=7.65, 2.38 Hz, 1H),4.87-5.01 (m, 1H), 4.51-4.61 (m, 1H), 3.72-3.83 (m, 2H), 3.36-3.44 (m,2H), 3.28 (s, 3H), 2.49 (s, 3H), 1.97-2.07 (m, 2H), 1.75-1.86 (m, 2H),1.26 (d, J=6.27 Hz, 6H). MS (ESI) 450 (M+H).

Example 208 Preparation ofN-(4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)phenyl)isobutyramide

To a stirring solution of1-(4-aminophenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one(50 mg, 0.12 mmol) and Et₃N (0.052 mL, 0.37 mmol, Aldrich) in CH₂Cl₂ (1mL) at room temperature was added isobutyl chloride (0.014 mL, 0.136mmol, Aldrich). The reaction mixture was stirred at room temperature for1 h and then quenched with H₂O. The solvent was evaporated and the crudesolid was purified by flash chromatography (SiO₂, 0 to 10% MeOH inCH₂Cl₂) to yield 34.2 mg of the desired product as a white solid. ¹H NMR(400 MHz, CDCl₃) δ ppm 8.16 (s, 2H), 7.55-7.61 (m, 3H), 7.26-7.28 (m,2H), 7.20 (d, J=7.78 Hz, 1H), 5.98-6.05 (m, 1H), 5.92-5.98 (m, 1H),4.52-4.59 (m, 1H), 4.14-4.22 (m, 2 H), 3.57-3.66 (m, 2H), 2.47-2.57 (m,1H), 2.37-2.42 (m, 2H), 2.03-2.11 (m, 2 H), 1.78-1.87 (m, 2H), 1.48-1.69(m, 2H), 1.24 (d, J=6.78 Hz, 6H), 0.93 (t, J=7.28 Hz, 3H). MS (ESI) 476(M+H).

Example 209 Preparation of isopropyl4-(1-(4-isobutyramidophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Step A. Preparation of isopropyl4-(1-(4-aminophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Isopropyl4-(1-(4-aminophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatewas prepared according to procedures described in Example 189substituting tert-butyl 4-iodophenylcarbamate (Oakwood) for5-bromo-2-(methylsulfonyl)pyridine in Step B except that reaction washeated at 100° C. overnight and then heated at 140° C. for 6 h. Thecrude solid was purified by flash chromatography (SiO₂, 0 to 10% MeOH inCH₂Cl₂). MS (ESI) 372 (M+H).

Step B Example 209

Example 209 was prepared according to procedures described in Example208 substituting isopropyl4-(1-(4-aminophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatefor1-(4-aminophenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one.¹H NMR (400 MHz, CDCl₃) δ ppm 7.62 (br. s., 1H), 7.59 (d, J=8.78 Hz,2H), 7.25-7.30 (m, 2H), 7.22 (d, J=7.53 Hz, 1H), 6.00 (d, J=2.51 Hz,1H), 5.93-5.99 (m, 1H), 4.87-5.00 (m, 1H), 4.44-4.56 (m, 1H), 3.70-3.82(m, 2H), 3.33-3.43 (m, 2H), 2.45-2.61 (m, 1H), 1.94-2.07 (m, 2 H),1.72-1.87 (m, 2H), 1.22-1.29 (m, 12H). MS (ESI) 442 (M+H).

Example 210 Preparation ofN-(4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)phenyl)pivalamide,hydrochloride salt

Example 210 was prepared according to procedures described in Example208 substituting pivaloyl chloride (Aldrich) for isobutyl chloride andwas then converted to the hydrochloride salt by addition of 1 equivalentof HCl (1N HCl in Et₂O) to the compound stirring in CH₂Cl₂ for 5 minfollowed by concentration in vacuo to the desired product. ¹H NMR (400MHz, CDCl₃) δ ppm 8.17 (s, 2H), 7.61-7.67 (m, 2H), 7.49 (s, 1H),7.29-7.35 (m, 2H), 7.22 (d, J=7.53 Hz, 1H), 5.95-6.04 (m, 2H), 4.52-4.62(m, 1H), 4.15-4.26 (m, 2H), 3.58-3.68 (m, 2H), 2.41 (t, J=7.53 Hz, 2H),2.04-2.14 (m, 2H), 1.79-1.90 (m, 2H), 1.52-1.64 (m, 2H), 1.33 (s, 9H),0.95 (t, J=7.28 Hz, 3H). MS (ESI) 490 (M+H).

Example 211 Preparation of isopropyl4-(2-oxo-1-(4-pivalamidophenyl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 211 was prepared according to procedures described in Example208 substituting isopropyl4-(1-(4-aminophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(prepared according to the procedure described in Step A of Example 209)for1-(4-aminophenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-oneand substituting pivaloyl chloride (Aldrich) for isobutyl chloride. ¹HNMR (400 MHz, CDCl₃) δ ppm 7.61-7.67 (m, 2H), 7.51 (s, 1H), 7.28-7.34(m, 2H), 7.22 (d, J=7.53 Hz, 1H), 5.97-6.02 (m, 1H), 5.92-5.97 (m, 1H),4.87-4.99 (m, 1H), 4.45-4.53 (m, 1H), 3.71-3.81 (m, 2H), 3.33-3.43 (m,2H), 1.89-2.04 (m, 2H), 1.73-1.89 (m, 2H), 1.33 (s, 9H), 1.26 (d, J=6.27Hz, 6H). MS (ESI) 456 (M+H).

Example 212 Preparation of2,2,2-trifluoro-N-(4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)phenyl)acetamide,TFA salt

Example 212 was prepared according to procedures described in Example208 substituting 2,2,2-trifluoroacetic anhydride (Aldrich) for isobutylchloride except that the crude product was purified by preparative HPLC(C₁₈ column, 10-100% MeOH in water containing 0.1% trifluoroaceticacid). ¹H NMR (500 MHz, DMSO-d6) δ ppm 11.43 (br. s., 1H), 8.24 (s, 2H),7.76 (d, J=8.80 Hz, 2H), 7.56 (d, J=7.70 Hz, 1H), 7.42 (d, J=8.80 Hz,2H), 5.98-6.10 (m, 2H), 4.69-4.83 (m, 1H), 4.16-4.28 (m, 2H), 3.41-3.56(m, 2H), 2.32-2.41 (m, 2H), 1.95-2.10 (m, 2H), 1.43-1.66 (m, 4H), 0.88(t, J=7.15 Hz, 3H). MS (ESI) 502 (M+H).

Example 214 Preparation ofcis-1-(4-(methylsulfonyl)phenyl)-4-((1r,4r)-4-(pyrimidin-2-yl)cyclohexyloxy)pyridin-2(1H)-one,TFA salt

Step A. Preparation of 4-(benzyloxy)cyclohexanecarbonitrile

To a solution of 4-(benzyloxy)cyclohexanone (2.94 g, 14.39 mmol,prepared according to procures described in Goodman et al., U.S. PatentApplication Publication No. 2006/0292073 A1) in 1,2-dimethoxyethane(14.39 mL, Aldrich) was added tosylmethyl isocyanide (5.62 g, 28.8 mmol,Aldrich) in one portion. The resulting mixture was cooled to 0° C. andpotassium t-butoxide solution (3.82 mL, 3.82 mmol, 1.0 M in2-methyl-2-propanol, Aldrich) was added dropwise. The reaction mixturewas stirred at 0° C. for 10 min and at room temperature for 5 hrs andthen quenched with 1N HCl (45 mL). The aqueous layer was extractedfurther with EtOAc (3×). The combined organic extracts were washed withbrine, dried (MgSO₄) and evaporated under reduced pressure. The residuewas purified by flash chromatography on silica gel (0-40% EtOAc/hexanes)to give a cis and trans mixture of 4-(benzyloxy)cyclohexanecarbonitrile(2.14 g, 69%) as a light orange oil. MS (ESI) 216 (M+H).

Step B. Preparation of 4-(benzyloxy)cyclohexanecarboximidamide

To a solution of 4-(benzyloxy)cyclohexanecarbonitrile (1.12 g, 5.20mmol) in EtOH (8.0 mL) at 0° C. was bobbled HCl gas (Aldrich) for 35 minand the resulting mixture was continuously stirred at 0° C. for 1 hr andthen evaporated under reduced pressure. The residue was dissolved inEtOH (6.0 mL) followed by addition of NH₃/MeOH (7.0 M, Aldrich) at 0° C.After stirring at room temperature for 30 min, the mixture wasevaporated and the residue was partitioned between 4N NaOH andchloroform. The aqueous layer was extracted further with chloroform(3×). The combined organic layers were washed with water/brine (1:1),dried (MgSO₄) and evaporated under reduced pressure to yield a cis andtrans mixture of 4-(benzyloxy)cyclohexanecarboximidamide (1.193 g, 99%)as a light yellow gum. This crude product was used in the next stepwithout further purification. MS (ESI) 233 (M+H).

Step C. Preparation of 2-(4-(benzyloxy)cyclohexyl)pyrimidine

A mixture of 4-(benzyloxy)cyclohexanecarboximidamide (330 mg, 1.420mmol) and (E)-3-(dimethylamino)acrylaldehyde (0.568 mL, 5.68 mmol,Aldrich) in pyridine (6.0 mL) was heated at 100° C. for 3 hrs andevaporated under reduced pressure. The residue was then partitionedbetween ether and water. The aqueous layer was extracted further withether (3×) and the combined extracts were washed with water and brine,dried (Na₂SO₄) and concentrated in vacuo. The crude product was purifiedby flash chromatography on silica gel (0-100% EtOAc/hexanes) to give acis and trans mixture of 2-(4-(benzyloxy)cyclohexyl)pyrimidine (239.3mg, 62.8%) as a colorless oil. MS (ESI) 269 (M+H).

Step D. Preparation of 4-(pyrimidin-2-yl)cyclohexanol

To a solution of 2-(4-(benzyloxy)cyclohexyl)pyrimidine (289.9 mg, 1.080mmol) in CH₂Cl₂ (25 mL) and water (1.0 mL) at room temperature was added2,3-dichloro-5,6-dicyano-1,4-benzoquinone (392 mg, 1.728 mmol, Aldrich).The reaction mixture was heated at 40° C. for 10 hrs, cooled to roomtemperature and diluted with CH₂Cl₂ and NaHCO₃ aqueous solution. Theaqueous layer was extracted further with CH₂Cl₂ (3×) and the combinedextracts were washed with brine, dried (Na₂SO₄) and evaporated underreduced pressure. The residue was purified by flash chromatography onsilica gel (0-15% MeOH/CH₂Cl₂) to give a cis and trans mixture of4-(pyrimidin-2-yl)cyclohexanol (157.5 mg, 82%) as an orange oil. MS(ESI) 179 (M+H).

Step E Example 214

A mixture of 4-hydroxy-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one(53.1 mg, 0.200 mmol, Example 1), 4-(pyrimidin-2-yl)cyclohexylmethanesulfonate (51.3 mg, 0.2 mmol, prepared according to proceduresdescribed at Step C of Example 1 substituting4-(pyrimidin-2-yl)cyclohexanol fortert-butyl-4-hydroxy-1-piperidinecarboxylate) and potassium carbonate(55.3 mg, 0.400 mmol) in DMF (1.0 mL) was heated at 140° C. for 3 hrsand 100° C. overnight and cooled to room temperature. The mixture wasdiluted with EtOAc and water and the aqueous layer was extracted furtherwith EtOAc (4×). The combined organic layers were washed withbrine/water (1:1, 2×), dried (Na₂SO₄) and evaporated under reducedpressure. The residue was purified first by preparative HPLC (C₁₈column; 0-90% methanol in water containing 0.05% trifluoroacetic acid)followed by further purification by preparative HPLC (C₁₈ column; 0-90%acetonitrile in water containing 0.05% trifluoroacetic acid) to providecis isomer of Example 214 (16.1 mg, yellow solid, 18%) uponlyophilization. ¹H NMR (500 MHz, CDCl₃) δ 8.91 (d, J=5.50 Hz, 2 H), 8.09(d, J=8.25 Hz, 2H), 7.62 (d, J=8.25 Hz, 2H), 7.32 (d, J=7.70 Hz, 1H),6.31-6.36 (m, 2H), 4.74 (app brs, 1H), 3.13-3.22 (m, 1H), 3.11 (s, 3H),2.23-2.30 (m, 2H), 2.08-2.22 (m, 2H), 1.90-1.98 (m, 2H), 1.81-1.90 (m,2H). MS (ESI) 426 (M+H).

Example 215 Preparation oftrans-1-(4-(methylsulfonyl)phenyl)-4-((1r,4r)-4-(pyrimidin-2-yl)cyclohexyloxy)pyridin-2(1H)-one,TFA salt

Example 215 was prepared as described above in Example 214 and wasseparated from the cis-isomer by preparative HPLC at Step E to yield thetitle compound. ¹H NMR (500 MHz, CDCl₃). δ 8.79 (d, J=4.95 Hz, 2H), 8.08(d, J=8.80 Hz, 2H), 7.62 (d, J=8.25 Hz, 2H), 7.23-7.31 (m, 2H), 6.19 (d,J=2.75 Hz, 1H), 6.15 (dd, J=7.70, 2.20 Hz, 1H), 4.32-4.44 (m, 1H), 3.10(s, 3H), 2.99-3.09 (m, 1H), 2.31-2.40 (m, 2H), 2.16-2.23 (m, 2H),1.80-1.93 (m, 2H), 1.62-1.75 (m, 2 H). MS (ESI) 426 (M+H).

Example 217 Preparation of1,1,1-trifluoro-N-(4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)phenyl)methanesulfonamide,TFA salt

Example 217 was prepared according to procedures described in Example212 substituting trifluoromethanesulfonic anhydride (Aldrich) for2,2,2-trifluoroacetic anhydride. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.42 (s,2H), 7.30 (d, J=7.53 Hz, 1 H), 7.16-7.27 (m, 4H), 6.28 (d, J=2.26 Hz,1H), 6.19 (dd, J=7.78, 2.51 Hz, 1H), 4.71-4.79 (m, 1H), 4.03-4.14 (m,2H), 3.92-4.03 (m, 2H), 2.54 (t, J=7.53 Hz, 2 H), 2.09-2.21 (m, 2H),1.97-2.09 (m, 2H), 1.60-1.71 (m, 2H), 1.00 (t, J=7.28 Hz, 3H). MS (ESI)538 (M+H).

Example 218 Preparation ofN,N-dimethyl-4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)benzenesulfonamide,hydrochloride salt

Example 218 was prepared according to procedures described in Example187 substituting 4-bromo-N,N-dimethylbenzenesulfonamide (Alfa-Aesar) for5-bromo-2-(methylsulfonyl)pyridine and was then converted to thehydrochloride salt by addition of 1 equivalent of HCl (1N HCl in Et₂O)to the compound stirring in CH₂Cl₂ for 5 min followed by concentrationin vacuo to the desired product. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.39 (br.s., 2H), 7.92 (d, J=8.53 Hz, 2H), 7.61 (d, J=8.53 Hz, 2H), 7.29-7.33 (m,1H), 6.09 (d, J=8.78 Hz, 1H), 5.96-6.05 (m, 1H), 4.65-4.79 (m, 1H),4.07-4.31 (m, 4H), 2.80 (s, 6H), 2.54 (t, J=7.53 Hz, 2H), 2.06-2.22 (m,4H), 1.60-1.70 (m, 2H), 0.99 (t, J=7.28 Hz, 3H). MS (ESI) 498 (M+H).

Example 221 Preparation of1-(4-(methylsulfonyl)phenyl)-6-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)-1,6-dihydropyridine-3-carbonitrile,TFA salt

Step A. Preparation of4-hydroxy-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridine-3-carbonitrile

A mixture of 4-hydroxy-6-oxo-1,6-dihydropyridine-3-carbonitrile (200 mg,1.469 mmol, Medinoah), 1-bromo-4-(methylsulfonyl)benzene (345 mg, 1.469mmol), 4,7-dimethoxy-1,10-phenanthroline (70.6 mg, 0.294 mmol),copper(I) iodide (56.0 mg, 0.294 mmol) and potassium carbonate (609 mg,4.41 mmol) in DMSO (3 mL) was heated at 190° C. To the reaction mixturewas added H₂O (10 mL) and the pH adjusted to ˜2 using with 1N HCl. Theresulting aqueous mixture was extracted with EtOAc (40 mL, 2×). Thecombined extracts were dried over Na₂SO₄ and concentrated to give abrown oil. The crude oil was purified by flash chromatography (SiO₂,0-5% MeOH/CH₂Cl₂) to give a yellow solid (35 mg, 0.084 mmol, 5.74%). MS(ESI) 291 (M+H).

Step B Example 221

A stirred mixture of 1-(5-propylpyrimidin-2-yl)piperidin-4-ylmethanesulfonate (46.4 mg, 0.155 mmol),4-hydroxy-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridine-3-carbonitrile(30 mg, 0.103 mmol) and cesium carbonate (67.3 mg, 0.207 mmol) in DMF(1.5 mL) was heated at 120° C. for 16 h and then cooled to roomtemperature. The resulting mixture was diluted with EtOAc and H₂O andthe aqueous layer was extracted with EtOAc (3×). The combined extractswere washed with H₂O, dried (Na₂SO₄) and evaporated. The residue waspurified by preparative HPLC (C₁₈ column; 20-90% MeOH in watercontaining 0.1% trifluoroacetic acid) to give Example 221 (5 mg, 10.13%)as an off-white solid. ¹H NMR (methylene-chloride) δ ppm 8.29-8.37 (m,2H), 8.09 (d, J=8.80 Hz, 2H), 7.85 (s, 1H), 7.59 (d, J=8.80 Hz, 2H),6.01 (s, 1H), 4.76 (d, J=3.30 Hz, 1H), 4.03-4.14 (m, 2H), 3.88-4.03 (m,2H), 3.09 (s, 3H), 2.48 (t, J=7.42 Hz, 2H), 1.94-2.19 (m, 4H), 1.52-1.69(m, 2H), 0.95 (t, J=7.42 Hz, 3H). MS (ESI) 494 (M+H).

Example 223 Preparation ofN-tert-butyl-4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)benzenesulfonamide

Example 223 was prepared according to procedures described in Example187 substituting 4-bromo-N-tert-butylbenzenesulfonamide (Combi-Blocks)for 5-bromo-2-(methylsulfonyl)pyridine. ¹H NMR (400 MHz, CDCl₃) δ ppm8.18 (s, 2H), 8.00 (d, J=8.53 Hz, 2H), 7.53 (d, J=8.53 Hz, 2H), 7.23 (d,J=7.53 Hz, 1H), 6.05 (dd, J=7.65, 2.38 Hz, 1H), 6.01 (d, J=2.26 Hz, 1H),4.54-4.63 (m, 1H), 4.50 (s, 1H), 4.15-4.25 (m, 2H), 3.59-3.69 (m, 2H),2.42 (t, J=7.53 Hz, 2H), 2.03-2.15 (m, 2H), 1.79-1.91 (m, 2H), 1.53-1.66(m, 2H), 1.30 (s, 9H), 0.95 (t, J=7.28 Hz, 3H). MS (ESI) 526 (M+H).

Example 224 Preparation of5-chloro-1-(3-fluoro-4-(methylsulfonyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one,TFA salt

Step A. Preparation of5-chloro-1-(3-fluoro-4-(methylsulfonyl)phenyl)-4-hydroxypyridin-2(1H)-one

5-Chloro-1-(3-fluoro-4-(methylsulfonyl)phenyl)-4-hydroxypyridin-2(1H)-onewas prepared according to procedures described in Example 263 Step Bsubstituting 4-bromo-2-fluoro-1-(methylsulfonyl)benzene (preparedaccording to the procedure described in Step D of Example 173substituting 4-bromo-2-fluoro-1-iodobenzene for4-bromo-1-iodo-2-methylbenzene) for 2-fluoro-4-iodobenzonitrile exceptthat the reaction was heated at 190° C. for 1 h. MS (ESI) 318 (M+H).

Step B Example 224

Example 224 was prepared according to procedures described in Example173 Step C substituting5-chloro-1-(3-fluoro-4-(methylsulfonyl)phenyl)-4-hydroxypyridin-2(1H)-onefor 4-hydroxypyridin-2(1H)-one except that the reaction was heated at140° C. for 6 h. The crude product was purified by preparative HPLC (C₁₈column, 10-100% MeOH in water containing 0.1% trifluoroacetic acid). ¹HNMR (400 MHz, CDCl₃) δ ppm 8.45 (s, 2H), 8.14 (t, J=7.91 Hz, 1H), 7.48(s, 1H), 7.35-7.47 (m, 2H), 6.27 (s, 1H), 4.78-4.87 (m, 1H), 4.20-4.29(m, 2H), 3.90-4.02 (m, 2H), 3.28 (s, 3H), 2.55 (t, J=7.53 Hz, 2H),2.08-2.22 (m, 4H), 1.60-1.72 (m, 2H), 1.00 (t, J=7.28 Hz, 3H). MS (ESI)521 (M+H).

Example 225 Preparation of4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridine-3-carbonitrile,TFA salt

Example 225 was prepared according to the procedures described inExample 221 substituting 1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-ylmethanesulfonate for 1-(5-propylpyrimidin-2-yl)piperidin-4-ylmethanesulfonate in Step B. ¹H NMR (500 MHz, CDCl₃) δ ppm 8.37 (s, 2H),8.13 (d, J=8.25 Hz, 2H), 7.86 (s, 1H), 7.60 (d, J=8.80 Hz, 2H), 6.17 (s,1H), 4.84 (br. s., 1H), 4.35 (d, J=14.85 Hz, 2H), 3.93-4.01 (m, 2H),3.12 (s, 3H), 2.08-2.23 (m, 4H), 1.83-1.85 (m, 1H), 1.10-1.25 (m, 2H),0.74 (m, 2H). MS (ESI) 491 (M+H).

Example 226 Preparation of tert-butyl4-(5-chloro-1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 226 was prepared according to the procedures described inExample 221 substituting tert-butyl4-(methylsulfonyloxy)piperidine-1-carboxylate for1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yl methanesulfonate,2-(5-chloro-4-hydroxy-2-oxopyridin-1(2H)-yl)-5-(methylsulfonyl)benzene-1-yliumfor4-hydroxy-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridine-3-carbonitrilein Step B. ¹H NMR (500 MHz, CDCl₃) δ ppm 8.07 (d, J=8.25 Hz, 2H), 7.61(d, J=8.80 Hz, 2H), 7.42 (s, 1H), 6.03 (s, 1H), 4.52-4.68 (m, 1H),3.57-3.73 (m, 2H), 3.40-3.56 (m, 2H), 3.08 (s, 3H), 1.76-2.02 (m, 4H),1.46 (s, 9H). MS (ESI) 482 (M+H).

Example 227 Preparation of4-(5-chloro-2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)-2-fluorobenzonitrile

Example 227 was prepared according to procedures described in Example173 Step C substituting4-(5-chloro-4-hydroxy-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile(prepared according to the procedure described in Step B of example 263)for 4-hydroxypyridin-2(1H)-one except that the reaction was heated at140° C. for 5 h and the crude solid was purified by flash chromatography(SiO₂, O to 100% EtOAc in CH₂Cl₂). ¹H NMR (400 MHz, CDCl₃) δ ppm 8.18(s, 2H), 7.77 (dd, J=8.28, 6.78 Hz, 1H), 7.37-7.43 (m, 2H), 7.34 (dd,J=8.41, 1.63 Hz, 1H), 6.05 (s, 1 H), 4.63-4.71 (m, 1H), 3.96-4.14 (m,2H), 3.77-3.96 (m, 2H), 2.42 (t, J=7.53 Hz, 2H), 2.01-2.14 (m, 2H),1.88-2.01 (m, 2H), 1.53-1.62 (m, 2H), 0.95 (t, J=7.28 Hz, 3H). MS (ESI)468 (M+H).

Example 228 Preparation of4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)benzenesulfonamide

To a stirring solution ofN-tert-butyl-4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)benzenesulfonamide(23 mg, 0.044 mmol) in CH₂Cl₂ (1 mL) was added trifluoroacetic acid (0.4mL, 5 mmol, Aldrich). The reaction was stirred at room temperature for 2days and then concentrated in vacuo to a yellow oil. The oil waspurified by flash chromatography (SiO₂, 0 to 5% MeOH in CH₂Cl₂) to yield11 mg of the desired product as an off-white solid. ¹H NMR (400 MHz,CDCl₃) δ ppm 8.18 (s, 2H), 8.03 (d, J=8.53 Hz, 2H), 7.54 (d, J=8.28 Hz,2H), 7.23 (d, J=7.78 Hz, 1H), 6.07 (dd, J=7.65, 2.63 Hz, 1H), 6.03 (d,J=2.51 Hz, 1H), 4.56-4.65 (m, 1H), 4.16-4.25 (m, 2H), 3.60-3.71 (m, 2H),2.42 (t, J=7.53 Hz, 2H), 2.04-2.14 (m, 2H), 1.80-1.90 (m, 2H), 1.53-1.64(m, 2H), 0.95 (t, J=7.28 Hz, 3 H). MS (ESI) 470 (M+H).

Example 229 Preparation of4-(5-chloro-4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile

Step A. Preparation of 1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-ylmethanesulfonate

1-(5-Cyclopropylpyrimidin-2-yl)piperidin-4-yl methanesulfonate wasprepared according to procedures described in Example 173 Step A and Bsubstituting 2-chloro-5-cyclopropylpyrimidine for2-chloro-5-propylpyrimidine in Step A.

Step B Example 229

Example 229 was prepared according to procedures described in Example173 Step C substituting4-(5-chloro-4-hydroxy-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile(prepared according to the procedure described in Step B of Example 263)for 4-hydroxypyridin-2(1H)-one except that the reaction was heated at140° C. for 2 h and at 100° C. overnight. The crude solid was purifiedby flash chromatography (SiO₂, 0 to 100% EtOAc in CH₂Cl₂). ¹H NMR (400MHz, CDCl₃) δ ppm 8.15 (s, 2H), 7.77 (dd, J=8.28, 6.78 Hz, 1H),7.38-7.43 (m, 2H), 7.34 (dd, J=8.41, 1.88 Hz, 1H), 6.05 (s, 1H),4.63-4.71 (m, 1H), 4.01-4.11 (m, 2H) 3.79-3.88 (m, 2H), 2.00-2.11 (m,2H), 1.88-2.00 (m, 2H), 1.69-1.79 (m, 1H), 0.89-0.96 (m, 2H), 0.56-0.66(m, 2H). MS (ESI) 466 (M+H).

Example 230 Preparation of4-(4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile

Step A. Preparation of tert-butyl4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Tert-butyl 4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatewas prepared according to procedures described in Example 8 Step Bsubstituting tert-butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate(prepared according to the procedure described in Step C of Example 1)for isopropyl 4-(methylsulfonyloxy)piperidine-1-carboxylate. MS (ESI)295 (M+H).

Step B. Preparation of 4-(piperidin-4-yloxy)pyridin-2(1H)-one

4-(Piperidin-4-yloxy)pyridin-2(1H)-one was prepared according toprocedures described in Example 106 Step A substituting tert-butyl4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate fortert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate.MS (ESI) 195 (M+H).

Step C. Preparation of4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

4-(1-(5-Cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-onewas prepared according to procedures described in Example 106 Step Bsubstituting 2-chloro-5-cyclopropylpyrimidine for2-chloro-5-propylpyrimidine except that the crude solid was purified byflash chromatography (SiO₂, 100% EtOAc in CH₂Cl₂ and then 0 to 10% MeOHin CH₂Cl₂). MS (ESI) 313 (M+H).

Step D Example 230

Example 230 was prepared according to procedures described in Example173 Step E substituting 2-fluoro-4-iodobenzonitrile (Matrix scientific)for 4-bromo-2-methyl-1-(methylsulfonyl)benzene except that the reactionwas heated under microwave condition at 125° C. for 30 min. ¹H NMR (400MHz, CDCl₃) δ ppm 8.14 (s, 2H), 7.75 (dd, J=8.28, 7.03 Hz, 1H),7.31-7.43 (m, 2H), 7.21 (d, J=7.78 Hz, 1H), 6.07 (dd, J=7.65, 2.64 Hz,1H), 5.99 (d, J=2.51 Hz, 1H), 4.52-4.62 (m, 1H), 4.13-4.25 (m, 2H),3.56-3.71 (m, 2H), 1.96-2.12 (m, 2H), 1.78-1.91 (m, 2H), 1.65-1.78 (m,1H), 0.76-0.96 (m, 2H), 0.57-0.76 (m, 2H). MS (ESI) 432 (M+H).

Example 231 Preparation of4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-1-(3-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 231 was prepared according to procedures described in Example230 substituting 4-bromo-2-fluoro-1-(methylsulfonyl)benzene (preparedaccording to the procedure described in Step D of Example 173substituting 4-bromo-2-fluoro-1-iodobenzene for4-bromo-1-iodo-2-methylbenzene) for 2-fluoro-4-iodobenzonitrile in StepD except that the reaction was heated under microwave condition at 160°C. for 30 min. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.07 (s, 2H), 8.02 (t,J=7.91 Hz, 1H), 7.37 (dd, J=10.29, 1.76 Hz, 1H), 7.30 (dd, J=8.41, 1.88Hz, 1H), 7.15 (d, J=7.78 Hz, 1H), 6.01 (dd, J=7.65, 2.64 Hz, 1H), 5.93(d, J=2.51 Hz, 1H), 4.43-4.56 (m, 1H), 4.05-4.17 (m, 2H), 3.50-3.62 (m,2H), 3.19 (s, 3H), 1.89-2.07 (m, 2H), 1.70-1.89 (m, 2H), 1.60-1.70 (m,1H), 0.68-0.92 (m, 2H), 0.46-0.68 (m, 2H). MS (ESI) 485 (M+H).

Example 233 Preparation of5-bromo-4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one,TFA salt

Step A. Preparation of 3,5-dibromo-4-hydroxypyridin-2(1H)-one

To 4-hydroxypyridin-2(1H)-one (5.55 g, 50 mmol) was added 48% aqueoushydrobromic acid (50 mL, 921 mmol) to produce a pale tan solution.Bromine (5.67 mL, 110 mmol) was added to produce an amber solution.After 3 days a yellow precipitate had formed. To the reaction was added300 mL of water causing a thick white slurry to form which was stirredfor 1 hour. The reaction was filtered and washed with 4×50 mL of water.to yield product (13.506 g, 1.81 mmol, quantitative yield) as a whitepowder. MS (ESI) 190 (M+1).

Step B. Preparation of 5-bromo-4-hydroxypyridin-2(1H)-one

To 3,5-dibromo-4-hydroxypyridin-2(1H)-one (5.4 g, 20.08 mmol) in a 200mL recovery flask was added hydrogen bromide, (50 mL, 442 mmol, 48%aqueous) to produce an off-white suspension. To the reaction was addedaniline (1.830 mL, 20.08 mmol) to produce a pale tan suspension and themixture was stirred at 60° C. for 4 h. A white precipitate was formed.After cooling to room temperature, the solid was filtered and washedwith 25 mL of water to yield pure product (2.071 g, 10.9 mmol, 54%) as atan powder. The aqueous mixture was adjusted to pH ˜12 (pH paper) using21 mL of 50% aqueous NaOH, causing more off-white gelatinous precipitateto form. The precipitate was collected and washed with water to yieldadditional pure product (1.1 g, 29%). MS (ESI) 190 (M+H).

Step C. Preparation of5-bromo-4-hydroxy-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

The intermediate was prepared according to the procedures described inExample 221 substituting 5-bromo-4-hydroxypyridin-2(1H)-one for4-hydroxy-6-oxo-1,6-dihydropyridine-3-carbonitrile in Step A. MS (ESI)345 (M+H).

Step D Example 233

Example 233 was prepared according to the procedures described inExample 221 substituting5-bromo-4-hydroxy-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one for4-hydroxy-1-(4-(methylsulfonyl)phenyl)-6-oxo-1,6-dihydropyridine-3-carbonitrilein Step B. ¹H NMR (500 MHz, CDCl₃) δ ppm 8.36 (s, 2H), 8.11 (d, J=8.80Hz, 2H), 7.48-7.70 (m, 3H), 6.55 (s, 1H), 4.88 (s, 1H), 4.28 (d, J=13.75Hz, 2H), 3.92 (t, J=10.17 Hz, 2H), 3.11 (s, 3H), 2.06-2.25 (m, 4H),1.77-1.92 (m, 1H), 1.02-1.15 (m, 2H), 0.66-0.78 (m, 2H). MS (ESI) 494(M+H).

Example 235 Preparation of(E)-1-(2-fluoro-4-(methylsulfonyl)phenyl)-4-(1-(5-(prop-1-enyl)pyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Step A. Preparation of (E)-2-chloro-5-(prop-1-enyl)pyrimidine

To 5-bromo-2-chloropyrimidine (2.027 g, 10.48 mmol),(E)-prop-1-enylboronic acid (1.350 g, 15.72 mmol), PdCl₂(dppf)-CH₂Cl₂(0.428 g, 0.524 mmol), and potassium carbonate (4.35 g, 31.4 mmol) intoluene (20 mL) and water (0.5 mL) was bubbled nitrogen subsurface for 1minute and then placed in a 90° C. oil bath for 5 hours. 200 mL EtOAcwas added and the reaction was then washed with 3×200 mL of water, driedwith MgSO₄, filtered and concentrated to 1.53 g brown solids. This waspurified by flash chromatography (5% EtOAc in hexanes) to yield product(681 mg) as an off-white solid. MS (ESI) 155.7 (M+1).

Step B. Preparation of(E)-1-(5-(prop-1-enyl)pyrimidin-2-yl)piperidin-4-ol

Using (E)-2-chloro-5-(prop-1-enyl)pyrimidine (Ex. 235, Step A), the(E)-1-(5-(prop-1-enyl)pyrimidin-2-yl)piperidin-4-ol was prepared asdescribed in Example 142, Step A. MS (ESI) 220.2 (M+1).

Step C Preparation of Example 235

To 1-(2-fluoro-4-(methylsulfonyl)phenyl)-4-hydroxypyridin-2(1H)-one (28mg, 0.099 mmol) from Example 142, Step D,(E)-1-(5-(prop-1-enyl)pyrimidin-2-yl)piperidin-4-ol (26.0 mg, 0.119mmol) and triphenylphosphine (33.7 mg, 0.128 mmol) was added THF (0.5mL). To this white suspension was added diethyl azodicarboxylate (0.020mL, 0.128 mmol) to produce a yellow solution. A pale tan precipitateformed in 135 minutes. After 230 minutes, 2 mL ether was added. Thereaction was filtered and then washed with 3×1 mL of ether to giveExample 235 (24 mg. 0.049 mmol, 49%) as an off-white solid. ¹H NMR (500MHz, CDCl₃) δ ppm 1.81-1.86 (m, 1H) 1.88 (d, J=6.60 Hz, 4H) 2.08 (ddd,J=13.06, 3.71, 3.57 Hz, 2H) 3.12 (s, 3H) 3.64-3.73 (m, 2H) 4.16-4.24 (m,2H) 4.56-4.62 (m, 1H) 6.02 (d, J=2.20 Hz, 1H) 6.06-6.14 (m, 2H) 6.20 (d,1H) 7.13 (d, J=7.15 Hz, 1H) 7.64 (t, J=7.70 Hz, 1H) 7.80-7.93 (m, 2H)8.32 (s, 2H). MS (ESI) 485.2 (M+1).

Example 236 Preparation of(Z)-1-(2-fluoro-4-(methylsulfonyl)phenyl)-4-(1-(5-(prop-1-enyl)pyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 236 was prepared using the sequence described for Example 235and substituting (Z)-prop-1-enylboronic acid for (E)-prop-1-enylboronicacid in Step A. ¹H NMR (500 MHz, CDCl₃) δ ppm 1.77-1.97 (m, 3H)2.04-2.17 (m, 1H) 3.12 (s, 3H) 3.49 (q, J=6.78 Hz, 1H) 3.63-3.80 (m, 1H)4.11-4.30 (m, 1H) 4.60 (ddd, J=7.29, 3.85, 3.71 Hz, 1H) 5.79 (dq,J=11.55, 7.15 Hz, 1H) 6.03 (d, J=2.20 Hz, 1H) 6.09 (dd, J=7.70, 2.75 Hz,1H) 6.18 (d, J=11.55 Hz, 1H) 7.14 (d, J=7.70 Hz, 1H) 7.64 (t, J=7.70 Hz,1H) 7.79-7.95 (m, 1H) 8.33 (s, 1H). MS (ESI) 485.2 (M+1).

Example 238 Preparation of1-(4-amino-3-fluorophenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 238 was prepared according to procedures described in Example173 substituting 2-fluoro-4-iodoaniline (Aldrich) for4-bromo-2-methyl-1-(methylsulfonyl)benzene in Step E except thatreaction was heated under microwave condition at 100° C. for 30 min andthen at 130° C. at 30 min. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.18 (s, 2H),7.20 (d, J=7.53 Hz, 1H), 7.07 (dd, J=11.29, 2.26 Hz, 1 H), 6.92-6.99 (m,1H), 6.80-6.88 (m, 1H), 6.01 (d, J=2.51 Hz, 1H), 5.97 (dd, J=7.53, 2.51Hz, 1H), 4.51-4.62 (m, 1H), 4.15-4.28 (m, 2H), 3.88 (br. s., 2H),3.57-3.69 (m, 2H), 2.42 (t, J=7.53 Hz, 2H), 1.97-2.18 (m, 2H), 1.77-1.97(m, 2 H), 1.53-1.66 (m, 2H), 0.96 (t, J=7.28 Hz, 3H). MS (ESI) 424(M+H).

Example 239 Preparation ofN-(2-fluoro-4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)phenyl)pivalamide

Example 239 was prepared according to procedures described in Example208 substituting1-(4-amino-3-fluorophenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-onefor1-(4-aminophenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-oneand substituting pivaloyl chloride (Aldrich) for Isobutyryl chlorideexcept that the crude solid purified by flash chromatography (SiO₂, 0 to100% EtOAc in CH₂Cl₂). ¹H NMR (400 MHz, CDCl₃) δ ppm 8.51 (t, J=8.66 Hz,1H), 8.19 (s, 2H), 7.68 (d, J=3.51 Hz, 1H), 7.25-7.30 (m, 1H), 7.17-7.25(m, 1H), 7.12 (d, J=8.78 Hz, 1H), 5.96-6.06 (m, 2H), 4.51-4.63 (m, 1H),4.15-4.26 (m, 2H), 3.59-3.69 (m, 2H), 2.43 (t, J=7.53 Hz, 2H), 1.97-2.15(m, 2 H), 1.79-1.97 (m, 2H), 1.54-1.65 (m, 2H), 1.36 (s, 9H), 0.96 (t,J=7.28 Hz, 3H). MS (ESI) 508 (M+H).

Example 240 Preparation ofN-(2-fluoro-4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)phenyl)isobutyramide

Example 240 was prepared according to procedures described in Example208 substituting1-(4-amino-3-fluorophenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-onefor1-(4-aminophenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-oneexcept that the crude solid purified by flash chromatography (SiO₂, 0 to100% EtOAc in CH₂Cl₂). ¹H NMR (400 MHz, CDCl₃) δ ppm 8.54 (t, J=8.66 Hz,1H), 8.43 (s, 2H), 7.46 (d, J=3.26 Hz, 1H), 7.32 (d, J=7.53 Hz, 1H),7.25 (dd, J=11.42, 2.38 Hz, 1H), 7.12 (d, J=8.78 Hz, 1H), 6.39 (d,J=2.51 Hz, 1H), 6.18 (dd, J=7.65, 2.64 Hz, 1H), 4.67-4.77 (m, 1H),4.05-4.18 (m, 2H), 3.93-4.05 (m, 2H), 2.57-2.70 (m, 1H), 2.53 (t, J=7.53Hz, 2H), 2.10-2.21 (m, 2 H), 1.97-2.10 (m, 2H), 1.59-1.71 (m, 2H), 1.31(d, J=7.03 Hz, 6H), 1.00 (t, J=7.28 Hz, 3H). MS (ESI) 494 (M+H).

Example 241 Preparation of2,2,2-trifluoro-N-(2-fluoro-4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)phenyl)acetamide

Example 241 was prepared according to procedures described in Example239 substituting 2,2,2-trifluoroacetic anhydride (Aldrich) for pivaloylchloride. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.29-8.42 (m, 2H), 8.19 (s, 2H),7.36 (dd, J=11.17, 2.38 Hz, 1H), 7.16-7.25 (m, 2H), 6.05 (dd, J=7.65,2.64 Hz, 1H), 6.02 (d, J=2.51 Hz, 1H), 4.53-4.65 (m, 1H), 4.15-4.26 (m,2H), 3.60-3.71 (m, 2H), 2.43 (t, J=7.53 Hz, 2H), 2.00-2.15 (m, 2H),1.75-1.98 (m, 2H), 1.52-1.66 (m, 2H), 0.96 (t, J=7.40 Hz, 3H). MS (ESI)520 (M+H).

Example 242 Preparation ofN-methyl-N-(4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)phenyl)pivalamide

To a stirring suspension of sodium hydride (9.1 mg, 0.23 mmol),N-(4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)phenyl)pivalamide(15 mg, 0.030 mmol) in DMF (2 mL) was added Methyl iodide (10 μL, 0.16mmol). The reaction was stirred at room temperature for 1.5 h. Thereaction was quenched with H₂O and extracted with EtOAc. The organiclayer was concentrated in vacuo to a white solid. The solid was purifiedby flash chromatography (SiO₂, 0 to 100% EtOAc in CH₂Cl₂) to yield 10 mgof the desired product as a white solid. ¹H NMR (400 MHz, CDCl₃) δ ppm8.19 (s, 2H), 7.39-7.48 (m, 2H), 7.32-7.39 (m, 2H), 7.26 (d, J=2.01 Hz,1H), 5.98-6.09 (m, 2H), 4.55-4.64 (m, 1H), 4.16-4.28 (m, 2H), 3.59-3.71(m, 2H), 3.27 (s, 3H), 2.43 (t, J=7.40 Hz, 2H), 1.98-2.22 (m, 2H),1.74-1.98 (m, 2H), 1.53-1.66 (m, 2H), 1.12 (s, 9 H), 0.96 (t, J=7.28 Hz,3H). MS (ESI) 504 (M+H).

Example 243 Preparation of4-(1-(5-cyclobutylpyrimidin-2-yl)piperidin-4-yloxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Step A. Preparation of 2-chloro-5-cyclobutylpyrimidine

To a 100 mL recovery flask containing 5-bromo-2-chloropyrimidine (816mg, 4.22 mmol) was applied vacuum then placed under a nitrogenatmosphere. To the flask was added dichloromethane (3 mL),PdCl₂(dppf)-CH₂Cl₂ (172 mg, 0.211 mmol) and then cyclobutylzinc(II)bromide (8.44 mL, 4.22 mmol, 1.3 M in THF) over 1-2 minutes. Thereaction was quenched at 2 hours with 20 mL of saturated aqueous NH₄Cland 50 mL EtOAc. The organic layer was washed with 20 mL each ofsaturated aqueous NaHCO₃ and then NaCl, dried with MgSO₄, filtered andconcentrated to 0.88 g of yellow oil containing some solids. This waspurified by flash chromatography (5-10% EtOAc in hexanes) to yieldproduct (253 mg, 1.50 mmol, 36%) as a faintly pale yellow liquid withsome small amount of crystalline material. MS (ESI) 169.1 (M+1).

Step B. Preparation of 1-(5-cyclobutylpyrimidin-2-yl)piperidin-4-ol

This material was prepared as described in described in Example 142,Step A, substituting 2-chloro-5-cyclobutylpyrimidine for2-chloro-5-propylpyrimidine. MS (ESI) 234.2 (M+1).

Step C. Preparation of Example 243

To 1-(2-fluoro-4-(methylsulfonyl)phenyl)-4-hydroxypyridin-2(1H)-one(56.7 mg, 0.20 mmol), 1-(5-cyclobutylpyrimidin-2-yl)piperidin-4-ol (56.0mg, 0.240 mmol), and triphenylphosphine (68.2 mg, 0.260 mmol) added THF(1 mL) to produce a white suspension then added (E)-diethyldiazene-1,2-dicarboxylate (0.041 mL, 0.260 mmol) leading to a completedissolution of solids and produced a yellow solution within 1-2 minutes.After 55 minutes, with the reaction still a clear light yellow solution,added 5 mL of ether causing an off-white precipitate to form. Filteredafter stirring 5 minutes and washed with 4×1 mL of ether to yieldExample 243 (74 mg, 0.145 mmol, 73%) as an off-white powder. ¹H NMR (400MHz, CDCl₃) δ ppm 1.21 (t, J=7.03 Hz, 2H) 1.75-1.95 (m, 3H) 1.96-2.18(m, 5H) 2.25-2.40 (m, 2H) 3.12 (s, 3H) 3.38 (t, J=8.57 Hz, 1H) 3.48 (q,J=7.03 Hz, 1H) 3.58-3.70 (m, 2H) 4.21 (ddd, J=13.51, 6.92, 3.73 Hz, 2H)4.45-4.69 (m, 1H) 4.58 (ddd, J=7.58, 3.95, 3.84 Hz, 1H) 6.02 (d, J=2.64Hz, 1H) 6.08 (dd, J=7.91, 2.64 Hz, 1H) 7.13 (d, J=7.47 Hz, 1H) 7.51-7.70(m, 1H) 7.80-7.93 (m, 2H) 8.23 (s, 2H). MS (ESI) 499.2 (M+1).

Example 244 Preparation of4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)phthalonitrile

Example 244 was prepared according to procedures described in Example173 substituting 4-iodophthalonitrile (Aldrich) for4-bromo-2-methyl-1-(methylsulfonyl)benzene in Step E except thatreaction was heated under microwave condition at 140° C. for 30 min. ¹HNMR (400 MHz, CDCl₃) δ ppm 8.19 (s, 2H), 7.92-8.00 (m, 2H), 7.84 (dd,J=8.53, 2.01 Hz, 1H), 7.22 (d, J=7.53 Hz, 1H), 6.13 (dd, J=7.78, 2.51Hz, 1H), 6.01 (d, J=2.51 Hz, 1H), 4.55-4.65 (m, 1H), 4.16-4.27 (m, 2H),3.60-3.71 (m, 2H), 2.43 (t, J=7.53 Hz, 2H), 1.98-2.15 (m, 2H), 1.81-1.98(m, 2H), 1.54-1.66 (m, 2H), 0.96 (t, J=7.28 Hz, 3H). MS (ESI) 441 (M+H).

Example 245 Preparation of4-(4-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yloxy)-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile

Example 245 was prepared according to procedures described in Example230 substituting 2-chloro-5-ethylpyrimidine (Aldrich) for2-chloro-5-cyclopropylpyrimidine in Step C. In step D the reaction washeated under microwave condition at 140° C. for 30 min. ¹H NMR (400 MHz,CDCl₃) δ ppm 8.20 (s, 2H) 7.76 (dd, J=8.16, 6.90 Hz, 1H) 7.32-7.42 (m,2H) 7.21 (d, J=7.78 Hz, 1H) 6.07 (dd, J=7.65, 2.64 Hz, 1H) 6.00 (d,J=2.76 Hz, 1H) 4.53-4.62 (m, 1H) 4.14-4.26 (m, 2 H) 3.58-3.70 (m, 2H)2.49 (q, J=7.70 Hz, 2H) 1.97-2.14 (m, 2H) 1.76-1.97 (m, 2 H) 1.21 (t,J=7.53 Hz, 3H). MS (ESI) 420 (M+H).

Example 246 Preparation of4-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yloxy)-1-(3-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

Example 246 was prepared according to procedures described in Example230 substituting 2-chloro-5-ethylpyrimidine (Aldrich) for2-chloro-5-cyclopropylpyrimidine in Step C and substituting4-bromo-2-fluoro-1-(methylsulfonyl)benzene (prepared according to theprocedure described in Step D of Example 173 substituting4-bromo-2-fluoro-1-iodobenzene for 4-bromo-1-iodo-2-methylbenzene) for2-fluoro-4-iodobenzonitrile in Step D except that the reaction washeated under microwave condition at 160° C. for 30 min. ¹H NMR (400 MHz,CDCl₃) δ ppm 8.21 (s, 2H), 8.05-8.17 (m, 1H), 7.46 (dd, J=10.29, 1.76Hz, 1H), 7.38 (dd, J=8.28, 2.01 Hz, 1H), 7.23 (d, J=7.78 Hz, 1H), 6.10(dd, J=7.78, 2.51 Hz, 1H), 6.02 (d, J=2.51 Hz, 1H), 4.54-4.64 (m, 1H),4.16-4.27 (m, 2H), 3.60-3.71 (m, 2H), 3.27 (s, 3H), 2.50 (q, J=7.53 Hz,2H), 1.98-2.16 (m, 2H), 1.80-1.98 (m, 2H), 1.22 (t, J=7.65 Hz, 3H). MS(ESI) 473 (M+H).

Example 247 Preparation of4-(4-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yloxy)-2-oxopyridin-1(2H)-yl)-3-fluorobenzonitrile

Example 247 was prepared according to procedures described in Example190 substituting 2-chloro-5-ethylpyrimidine (Adlrich) for2-chloro-5-cyclopropylpyrimidine except that reaction was stirred at120° C. for 6 h. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.21 (s, 2H), 7.52-7.63(m, 3H), 7.12 (dd, J=7.78, 1.00 Hz, 1H), 6.08 (dd, J=7.78, 2.51 Hz, 1H),6.02 (d, J=2.51 Hz, 1H), 4.54-4.64 (m, 1 H), 4.17-4.26 (m, 2H),3.60-3.71 (m, 2H), 2.50 (q, J=7.61 Hz, 2H), 2.04-2.16 (m, 2H), 1.79-1.93(m, 2H), 1.22 (t, J=7.65 Hz, 3H). MS (ESI) 420 (M+H).

Example 248 Preparation of4-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yloxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

A suspension of4-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one (127 mg,0.424 mmol, prepared according to procedures described in Example 230Step C substituting 2-chloro-5-ethylpyrimidine (Aldrich) for2-chloro-5-cyclopropylpyrimidine), sodium hydride (60 wt % mineral oil,21 mg, 0.51 mmol) and DMF (5 mL) was purged with Argon and then stirredat room temperature for 1 h. To the reaction was added1,2-difluoro-4-(methylsulfonyl)benzene (90 mg, 0.47 mmol, MatrixScientific) and then heated at 110° C. for 1 h. The resulting mixturewas quenched with H₂O and extracted with EtOAc. The organic layer wasconcentrated in vacuo to a yellow solid. The solid was purified by flashchromatography (SiO₂, 0 to 100% EtOAc in CH₂Cl₂) to yield 91 mg of thedesired product as an off-white solid. ¹H NMR (400 MHz, CDCl₃) δ ppm8.20 (s, 2H), 7.83-7.91 (m, 2H), 7.64 (dd, J=8.53, 6.78 Hz, 1H), 7.13(dd, J=7.53, 1.00 Hz, 1H), 6.08 (dd, J=7.65, 2.64 Hz, 1 H), 6.03 (d,J=2.51 Hz, 1H), 4.54-4.63 (m, 1H), 4.16-4.27 (m, 2H), 3.60-3.70 (m, 2H),3.12 (s, 3H), 2.49 (q, J=7.53 Hz, 2H), 1.97-2.15 (m, 2H), 1.78-1.97 (m,2 H), 1.21 (t, J=7.53 Hz, 3H). MS (ESI) 473 (M+H).

Example 249 Preparation of1-(4-(2-hydroxybutylsulfonyl)phenyl)-4-(1-(pyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one,TFA salt

A suspension of (methylsulfonyl)phenyl)pyridin-2(1H)-one (104 mg, 0.206mmol) in THF (12 mL) was cooled to −78° C. and t-butyllithium (0.242 mL,0.411 mmol, 1.7 M in pentane) was added. The pale yellow fine suspensionbecame much thicker. After 30 minutes, propionaldehyde (0.030 mL, 0.411mmol) was added and then cooling bath was removed. The reaction wasquenched within 10 minutes with 20 mL of saturated aqueous NH₄Cl thenextracted with 30 mL of CH₂Cl₂. The organic layer was dried with MgSO₄,filtered and concentrated to give 102 mg of tan-yellow solids. Thismaterial was purified by preparative HPLC (C18, 10-90% MeOH in watercontaining 0.1% TFA) to give Example 249 (15 mg, 0.028 mmol, 14%) as apale yellow oil. ¹H NMR (400 MHz, CDCl₃) δ ppm 0.82-0.94 (m, 3H)1.41-1.58 (m, 2H) 1.76-1.96 (m, 2H) 1.93-2.15 (m, 2H) 3.13-3.40 (m, 6 H)3.64-3.80 (m, 2H) 3.95-4.18 (m, 2H) 4.48-4.71 (m, 1H) 6.00 (d, J=2.20Hz, 1 H) 6.05-6.17 (m, 1H) 6.54 (t, J=4.83 Hz, 1H) 7.25 (d, J=7.91 Hz,2H) 7.55 (d, J=8.35 Hz, 2H) 8.03 (d, J=8.79 Hz, 2H) 8.33 (d, J=4.83 Hz,1H). MS (ESI) 485.2 (M+1).

Example 250 Preparation of(Z)-5-chloro-1-(4-(methylsulfonyl)phenyl)-4-(1-(5-(prop-1-enyl)pyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one,TFA salt

To a mixture of5-chloro-4-hydroxy-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one (35 mg,0.117 mmol), (Z)-1-(5-(prop-1-enyl)pyrimidin-2-yl)piperidin-4-ol (30.7mg, 0.140 mmol, prepared as described in Example 236) andtriphenylphosphine (39.8 mg, 0.152 mmol) in THF (2 mL) was added(E)-diethyl diazene-1,2-dicarboxylate (0.024 mL, 0.125 mmol) slowly. Themixture was stirred at rt for 16 h. To the reaction mixture was addeddiethyl ether (10 mL). A precipitate was collected and washed withdiethyl ether (2×) to give Example 250 (5 mg, 8.55%) as a white solid.¹H NMR (500 MHz, CDCl₃) δ ppm 8.31-8.44 (m, 2H), 8.09 (d, J=8.25 Hz,2H), 7.63 (d, J=8.25 Hz, 2H), 7.43 (s, 1H), 6.18 (d, J=11.55 Hz, 1H),6.02-6.10 (m, 1H), 5.81-5.93 (m, 1H), 4.74 (br. s., 1H), 3.98-4.11 (m,4H), 3.49 (s, 3H), 3.09 (s, 3H), 2.07 (br. s., 4H). MS (ESI) 501 (M+H).

Example 251 Preparation of1-(3,4-difluorophenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Example 251 was prepared according to procedures described in Example244 substituting 1,2-difluoro-4-iodobenzene (Matrix Scientific) for4-iodophthalonitrile. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.19 (s, 2H),7.29-7.33 (m, 1 H), 7.24-7.28 (m, 1H), 7.20 (d, J=7.28 Hz, 1H), 7.13 (d,J=8.03 Hz, 1H), 5.88-6.18 (m, 2H), 4.49-4.68 (m, 1H), 4.09-4.32 (m, 2H),3.48-3.77 (m, 2H), 2.43 (t, J=7.40 Hz, 2H), 2.00-2.23 (m, 2H), 1.75-1.95(m, 2H), 1.47-1.70 (m, 2H), 0.96 (t, J=7.28 Hz, 3H). MS (ESI) 427 (M+H).

Example 252 Preparation of3,4-difluoro-2-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)benzonitrile

Example 252 was prepared according to procedures described in Example248 substituting4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one(prepared according to procedures described in Example 173 Step C) for4-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one andsubstituting 2,3,4-trifluorobenzonitrile (Oakwood) for1,2-difluoro-4-(methylsulfonyl)benzene. ¹H NMR (400 MHz, CDCl₃) δ ppm8.10 (s, 2H), 7.43-7.60 (m, 1H), 7.27-7.43 (m, 1 H), 7.02 (d, J=7.78 Hz,1H), 6.05 (dd, J=7.65, 2.64 Hz, 1H), 5.96 (d, J=2.51 Hz, 1 H), 4.43-4.60(m, 1H), 4.08-4.24 (m, 2H), 3.49-3.66 (m, 2H), 2.34 (t, J=7.53 Hz, 2H),1.99-2.08 (m, 2H), 1.71-1.88 (m, 2H), 1.43-1.59 (m, 2H), 0.87 (t, J=7.28Hz, 3H). MS (ESI) 452 (M+H).

Example 253 Preparation of2,3-difluoro-4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)benzonitrile

Example 253 was prepared according to procedures described in Example248 substituting4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one(prepared according to procedures described in Example 173 Step C) for4-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one andsubstituting 2,3,4-trifluorobenzonitrile (Oakwood) for1,2-difluoro-4-(methylsulfonyl)benzene. ¹H NMR (400 MHz, CDCl₃) δ ppm8.10 (s, 2H), 7.35-7.53 (m, 1H), 7.21-7.35 (m, 1H), 7.03 (d, J=7.03 Hz,1H), 6.01 (dd, J=7.65, 2.64 Hz, 1H), 5.93 (d, J=2.51 Hz, 1 H), 4.43-4.54(m, 1H), 4.05-4.19 (m, 2H), 3.50-3.66 (m, 2H), 2.34 (t, J=7.53 Hz, 2H),1.93-2.11 (m, 2H), 1.72-1.83 (m, 2H), 1.42-1.56 (m, 2H), 0.87 (t, J=7.28Hz, 3H). MS (ESI) 452 (M+H).

Example 254 Preparation of4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)-2-(trifluoromethyl)benzonitrile

Example 254 was prepared according to procedures described in Example244 substituting 4-iodo-2-(trifluoromethyl)benzonitrile (Aldrich) for4-iodophthalonitrile. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.19 (s, 2H), 7.98(d, J=8.28 Hz, 1H), 7.88 (d, J=2.01 Hz, 1H), 7.80 (dd, J=8.28, 2.01 Hz,1H), 7.24 (d, J=7.78 Hz, 1H), 6.12 (dd, J=7.65, 2.64 Hz, 1H), 6.02 (d,J=2.51 Hz, 1H), 4.55-4.65 (m, 1 H), 4.14-4.28 (m, 2H), 3.60-3.73 (m,2H), 2.43 (t, J=7.53 Hz, 2H), 2.05-2.15 (m, 2H), 1.80-1.93 (m, 2H),1.53-1.66 (m, 2H), 0.96 (t, J=7.28 Hz, 3H). MS (ESI) 484 (M+H).

Example 255 Preparation of4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)benzonitrile

Example 255 was prepared according to procedures described in Example244 substituting 4-iodobenzonitrile (Transworld) for4-iodophthalonitrile. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.19 (s, 2H),7.77-7.83 (m, 2H), 7.53-7.59 (m, 2H), 7.23 (d, J=7.53 Hz, 1H), 6.07 (dd,J=7.65, 2.64 Hz, 1H), 6.02 (d, J=2.51 Hz, 1H), 4.54-4.64 (m, 1H),4.16-4.28 (m, 2H), 3.59-3.70 (m, 2H), 2.43 (t, J=7.53 Hz, 2H), 1.98-2.17(m, 2H), 1.78-1.98 (m, 2H), 1.51-1.66 (m, 2H), 0.96 (t, J=7.40 Hz, 3H).MS (ESI) 416 (M+H).

Example 256 Preparation of2,5-difluoro-4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)benzonitrile

Example 256 was prepared according to procedures described in Example252 substituting 2,4,5-Trifluorobenzonitrile (Aldrich) for2,3,4-trifluorobenzonitrile. ¹H NMR (500 MHz, CDCl₃) δ ppm 8.13 (s, 2H),7.49 (dd, J=8.25, 5.50 Hz, 1H), 7.33 (dd, J=8.25, 5.50 Hz, 1H), 7.06 (d,J=7.70 Hz, 1H), 6.03 (dd, J=7.70, 2.20 Hz, 1H), 5.96 (d, J=2.75 Hz, 1H),4.48-4.59 (m, 1H), 4.10-4.20 (m, 2H), 3.52-3.69 (m, 2H), 2.37 (t, J=7.70Hz, 2H), 2.00-2.09 (m, 2H), 1.75-1.85 (m, 2H), 1.45-1.59 (m, 2H), 0.90(t, J=7.42 Hz, 3H). MS (ESI) 452 (M+H).

Example 257 Preparation ofcis-1-(4-(methylsulfonyl)phenyl)-4-(4-(5-propylpyrimidin-2-yl)cyclohexyloxy)pyridin-2(1H)-one,TFA salt

Step A. Preparation of 2-((dimethylamino)methylene)pentanal

To a solution of phosphorus oxychloride (2.330 mL, 25.00 mmol, Aldrich)in 1,2-dichloroethane (5.0 mL) at 0° C. was added DMF (7.74 mL, 100mmol, EMD) in 1,2-dichloroethane (10.0 mL) during the course of 10 min.The mixture was stirred at 0° C. for 20 min and then warmed up to roomtemperature. After stirring at room temperature for 3 hrs, valeraldehyde(2.66 mL, 25.0 mmol, Aldrich) in 1,2-dichloroethane (5.0 mL) was addeddropwise (5 min) and the resulting mixture was stirred at roomtemperature for 50 min and at 85° C. for 50 min. The cooled reactionmixture was poured into a mixture of ice and K₂CO₃ (7.5 g) followed byaddition of saturated K₂CO₃ aqueous solution until the pH of the mixturewas around 10. To the above mixture, dimethyl amine (8.0 mL, 40 wt. %solution in water, Aldrich) was added and the reaction mixture washeated at 80° C. for 1 hr, cooled and evaporated under reduced pressureto remove 1,2-dichloroethane. The resulting mixture was then heated at95° C. for 1 hr, cooled to room temperature and extracted with EtOAc(3×). The combined extracts were washed with brine, dried (Na₂SO₄) andconcentrated in vacuo. The residue was distilled under reduced pressure(1 torr at 145-155° C. of oil bath) to yield the title compound (200 mg,5.7%) as an orange oil. ¹H NMR (500 MHz, CDCl₃) δ 8.85 (s, 1H), 6.48 (s,1H), 3.13 (s, 6H), 2.30-2.45 (m, 2H), 1.32-1.53 (m, 2H), 0.93 (t, J=7.42Hz, 3H).

Step B Example 257

Example 257 was prepared according to procedures described in Example214 substituting 2-((dimethylamino)methylene)pentanal for(E)-3-(dimethylamino)acrylaldehyde at Step C. ¹H NMR (400 MHz, CDCl₃) δ8.59 (s, 2H), 8.08 (d, J=8.61 Hz, 2H), 7.64 (d, J=8.42 Hz, 2H), 7.24 (d,J=7.69 Hz, 1H), 6.16 (dd, J=7.69, 2.38 Hz, 1H), 6.05 (d, J=2.38 Hz, 1H),4.67 (app brs, 1H), 3.11 (s, 3H), 3.00-3.10 (m, 1H), 2.60 (t, J=7.60 Hz,2H), 2.07-2.29 (m, 4H), 1.90-1.98 (m, 2 H), 1.82 (t, J=13.37 Hz, 2H),1.63-1.75 (m, 2H), 1.01 (t, J=7.33 Hz, 3H). MS (ESI) 468 (M+H).

Example 258 Preparation oftrans-1-(4-(methylsulfonyl)phenyl)-4-(4-(5-propylpyrimidin-2-yl)cyclohexyloxy)pyridin-2(1H)-one,TFA salt

Example 258 was prepared as described above in Example 257 and wasseparated form the cis-isomer by preparative HPLC to yield the titlecompound. ¹H NMR (400 MHz, CDCl₃) δ 8.57 (s, 2H), 8.09 (d, J=8.61 Hz,2H), 7.64 (d, J=8.61 Hz, 2H), 7.24 (d, J=7.51 Hz, 1H), 6.03-6.13 (m,2H), 4.30-4.44 (m, 1H), 3.11 (s, 3H), 2.88-3.06 (m, 1H), 2.60 (t, J=7.69Hz, 2H), 2.30-2.41 (m, 2H), 2.24-2.36 (m, 2H), 2.14-2.26 (m, 2H),1.78-1.92 (m, 2H), 1.64-1.75 (m, 2H), 1.01 (t, J=7.33 Hz, 3H). MS (ESI)468 (M+H).

Example 259 Preparation of3-chloro-4-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)benzonitrile

Example 259 was prepared according to procedures described in Example252 substituting 3-chloro-4-fluorobenzonitrile (Aldrich) for2,3,4-trifluorobenzonitrile except that the reaction was heated at 80°C. for 3 h. ¹H NMR (500 MHz, CDCl₃) δ ppm 8.19 (s, 2H), 7.88 (d, J=1.76Hz, 1H), 7.72 (dd, J=8.16, 1.63 Hz, 1H), 7.53 (d, J=8.03 Hz, 1H), 7.04(d, J=7.53 Hz, 1H), 6.08 (dd, J=7.78, 2.51 Hz, 1H), 6.03 (d, J=2.26 Hz,1H), 4.54-4.66 (m, 1H), 4.13-4.32 (m, 2H), 3.57-3.72 (m, 2H), 2.43 (t,J=7.53 Hz, 2H), 2.05-2.19 (m, 2H), 1.79-2.00 (m, 2 H), 1.53-1.67 (m,2H), 0.96 (t, J=7.40 Hz, 3H). MS (ESI) 450 (M+H).

Example 260 Preparation of6-(2-oxo-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)nicotinonitrile

Example 260 was prepared according to procedures described in Example244 substituting 6-bromonicotinonitrile (Matrix Scientific) for4-iodophthalonitrile. ¹H NMR (400 MHz, CDCl₃) δ ppm 8.82 (d, J=1.76 Hz,1H), 8.35 (d, J=8.78 Hz, 1H), 8.19 (s, 2H), 8.08 (dd, J=8.66, 2.13 Hz,1H), 8.02 (d, J=8.03 Hz, 1H), 6.12 (dd, J=8.03, 2.51 Hz, 1H), 5.98 (d,J=2.51 Hz, 1H), 4.55-4.68 (m, 1H), 4.14-4.28 (m, 2H), 3.60-3.73 (m, 2H),2.43 (t, J=7.53 Hz, 2H), 1.99-2.18 (m, 2H), 1.77-1.99 (m, 2H), 1.51-1.66(m, 2H), 0.96 (t, J=7.28 Hz, 3H). MS (ESI) 417 (M+H).

Example 261 Preparation of1-(4-(methylsulfonyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)azepan-4-yloxy)pyridin-2(1H)-one,TFA salt

Example 261 was prepared according to procedures described in Example132 substituting tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)azepane-1-carboxylate(Example 6) for tert-butyl4-(2-oxo-1-(pyridin-3-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylateat Step C. ¹H NMR (400 MHz, CDCl₃) δ 8.44 (s, 2H), 8.08 (d, J=8.25 Hz,2H), 7.61 (d, J=8.25 Hz, 2H), 7.24 (d, J=7.15 Hz, 1H), 6.01-6.08 (m,2H), 4.55-4.61 (m, 1H), 3.90-4.04 (m, 3H), 3.77-3.88 (m, 1H), 3.10 (s,3H), 2.46-2.56 (m, 2H), 2.04-2.27 (m, 4H), 1.84-2.01 (m, 2H), 1.56-1.69(m, 2H), 0.98 (t, J=7.15 Hz, 3H). MS (ESI) 483 (M+H).

Example 262 Preparation of4-(1-(5-cyclopropylpyrimidin-2-yl)azepan-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one,TFA salt

Example 262 was prepared according to procedures described in Example132 substituting tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)azepane-1-carboxylatefor tert-butyl4-(2-oxo-1-(pyridin-3-yl)-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylateat Step C and 2-chloro-5-cyclopropylpyrimidine for2-chloro-5-propylpyrimidine at Step D. ¹H NMR (400 MHz, CDCl₃) δ 8.40(s, 2H), 8.08 (d, J=8.25 Hz, 2H), 7.61 (d, J=8.80 Hz, 2H), 7.25-7.28 (m,1H), 6.13 (d, J=2.20 Hz, 1H), 6.06 (dd, J=7.42, 2.47 Hz, 1H), 4.55-4.63(m, 1H), 3.87-4.03 (m, 3H), 3.78-3.88 (m, 1H), 3.10 (s, 3H), 2.03-2.28(m, 4 H), 1.86-2.00 (m, 2H), 1.77-1.89 (m, 1H), 1.02-1.07 (m, 2H),0.65-0.77 (m, 2 H). MS (ESI) 481 (M+H).

Example 263 Preparation of4-(5-chloro-2-oxo-4-(1-(5-(3,3,3-trifluoropropyl)pyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)-2-fluorobenzonitrile,TFA salt

Step A. Preparation of4-(5-chloro-4-hydroxy-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile

A mixture of 2-fluoro-4-iodobenzonitrile (4000 mg, 16.19 mmol),5-chloro-4-hydroxypyridin-2(1H)-one (2357 mg, 16.19 mmol),4,7-dimethoxy-1,10-phenanthroline (778 mg, 3.24 mmol), copper(I) iodide(617 mg, 3.24 mmol) and potassium carbonate (4476 mg, 32.4 mmol) in DMSO(40 mL) was stirred at 140° C. under N₂ for 3 h. After cooled to rt, thereaction mixture was diluted with H₂O (50 mL) and added 1N HCl to adjustthe pH to ˜2 (pH paper). The resulting mixture was extracted with EtOAc(400 mL, 2×). The combined extracts were dried (Na₂SO₄) and evaporatedunder reduced pressure to give black oil. The residue was purified byflash chromatography (SiO₂, 0 to 7% MeOH/CH₂Cl₂) to give brown oil (3.2g, 43.3%). MS (ESI) 265 (M+H).

Step B. Preparation of tert-butyl4-(5-chloro-1-(4-cyano-3-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

The intermediate was prepared according to the procedures described inExample 221 substituting4-(5-chloro-4-hydroxy-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile for4-hydroxy-6-oxo-1,6-dihydropyridine-3-carbonitrile and tert-butyl4-(methylsulfonyloxy)piperidine-1-carboxylate for1-(5-propylpyrimidin-2-yl)piperidin-4-yl methanesulfonate in Step B. MS(ESI) 392 (M+H).

Step C. Preparation of4-(5-chloro-2-oxo-4-(piperidin-4-yloxy)pyridin-1(2H)-yl)-2-fluorobenzonitrile

A suspension of tert-butyl4-(5-chloro-1-(4-cyano-3-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate(2.2 g, 4.18 mmol) in MeOH (15 mL) was added hydrogen chloride (4M in1,4-dioxane) (0.609 g, 16.70 mmol) and stirred at rt. After 6 hstirring, solvent MeOH was evaporated and the resulting crude wasdiluted with EtOAc (50 mL). After saturated aqueous NaHCO₃ was added toadjust PH>7, the resulting mixture was vigorously stirred for 2 h. Theorganic layers was collected and the aqueous layer was back-extractedwith EtOAc 2×. The combined extracts were dried (Na₂SO₄) and evaporatedunder reduced pressure to give a brown solid as a crude product (1 g,2.88 mmol). MS (ESI) 348 (M+H).

Step D Example 263

A mixture of4-(5-chloro-2-oxo-4-(piperidin-4-yloxy)pyridin-1(2H)-yl)-2-fluorobenzonitrile(50 mg, 0.144 mmol), 2-chloro-5-(3,3,3-trifluoropropyl)pyrimidine (60.6mg, 0.288 mmol, prepared as described in Example 181) and potassiumcarbonate (59.6 mg, 0.431 mmol) in DMF (0.4 mL) was stirred at 90° C. ina closed vial for 24 h. After cooled to rt, the reaction mixture wasdiluted with EtOAc (60 mL) and H₂O (40 mL). The aqueous phase wasacidified by 1N HCl to PH=2. The organic extract was collected, driedover Na₂SO₄ and evaporated to give brown oil. The crude oil was purifiedby preparative HPLC (C₁₈ column; 20-90% MeOH in water containing 0.05%trifluoroacetic acid) to give Example 263 as a brown solid (5 mg,6.33%). ¹H NMR (500 MHz, CDCl₃) δ ppm 8.50 (s, 2H), 7.80 (t, J=7.42 Hz,1 H), 7.48 (s, 1H), 7.36 (dd, J=18.42, 8.52 Hz, 2H), 6.41 (s, 1H), 4.84(br. s., 1H), 4.29 (d, J=12.65 Hz, 2H), 3.89-4.05 (m, 2H), 2.79-2.92 (m,2H), 2.34-2.52 (m, 2 H), 2.16 (br. s., 4H). MS (ESI) 522 (M+H).

Example 264 Preparation of4-(5-chloro-4-(1-(5-fluoropyrimidin-2-yl)piperidin-4-yloxy)-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile,TFA salt

Example 264 was prepared according to the procedures described inExample 263 substituting 2-chloro-5-fluoropyrimidine for2-chloro-5-(3,3,3-trifluoropropyl)pyrimidine for2-chloro-5-(3,3,3-trifluoropropyl)pyrimidine in Step 4. ¹H NMR (500 MHz,CDCl₃) δ ppm 8.24 (s, 2H), 7.75-7.80 (m, 1H), 7.42 (s, 1H), 7.38 (d,J=9.35 Hz, 1H), 7.34 (d, J=8.25 Hz, 1H), 6.18 (s, 1H), 4.67-4.73 (m,1H), 4.01 (td, J=8.80, 3.85 Hz, 2H), 3.85-3.93 (m, 2H), 2.06 (dt,J=8.80, 4.40 Hz, 2H), 1.96 (td, 2H). MS (ESI) 444 (M+H).

Example 265 Preparation of4-(5-chloro-4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)-2-oxopyridin-1(2H)-yl)-3-fluorobenzonitrile

Step A. Preparation of5-chloro-4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

To a stirring mixture of 5-chloro-4-hydroxypyridin-2(1H)-one (212 mg,1.46 mmol), 1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-ol (320 mg, 1.459mmol, prepared according to procedures described in Example 173 Step Asubstituting 2-chloro-5-cyclopropylpyrimidine for2-chloro-5-propylpyrimidine) and triphenylphosphine (574 mg, 2.19 mmol)in DMF (10 mL) at 0° C. was added diisopropyl azodicarboxylate (0.43 mL,2.2 mmol). The reaction was stirred under Ar at room temperature for 2days and then H₂O was added. The resulting mixture was concentrated invacuo to a yellow oil. The oil was purified by flash chromatography(SiO₂, 0 to 100% EtOAc in CH₂Cl₂ and then SiO₂, 0 to 10% MeOH in CH₂Cl₂)to yield 153 mg of desired product as a white solid. MS (ESI) 347 (M+H).

Step B Example 265

Example 265 was prepared according to procedures described in Example252 substituting5-chloro-4-(1-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-onefor 4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one andsubstituting 3,4-difluorobenzonitrile (Aldrich) for2,3,4-trifluorobenzonitrile except that the reaction was heated at 110°C. for 3 days and then at 140° C. for 5 h. ¹H NMR (500 MHz, CDCl₃) δ ppm8.07 (s, 2H), 7.42-7.60 (m, 3 H), 7.23 (s, 1H), 5.99 (s, 1H), 4.50-4.69(m, 1H), 3.93-4.04 (m, 2H), 3.67-3.82 (m, 2H), 1.93-2.07 (m, 2H),1.78-1.92 (m, 2H), 1.61-1.72 (m, 1H), 0.78-0.91 (m, 2H), 0.47-0.61 (m,2H). MS (ESI) 466 (M+H).

Example 267 Preparation of tert-butyl4-(5-chloro-1-(4-cyano-3-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 267 was prepared according to procedures described in Example173 Step C substituting4-(5-chloro-4-hydroxy-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile(prepared according to the procedure described in Step B of Example 263)for 4-hydroxypyridin-2(1H)-one and substituting tert-butyl4-(methylsulfonyloxy)piperidine-1-carboxylate (prepared according to theprocedure described in Step C of Example 1) for1-(5-propylpyrimidin-2-yl)piperidin-4-yl methanesulfonate except thatthe crude product was purified by flash chromatography (SiO₂, 0 to 100%EtOAc in CH₂Cl₂). ¹H NMR (400 MHz, CDCl₃) δ ppm 7.77 (t, J=7.53 Hz, 1H),7.37-7.46 (m, 2H), 7.30-7.36 (m, 1H), 6.00 (s, 1H), 4.54-4.68 (m, 1H),3.58-3.71 (m, 2H), 3.40-3.56 (m, 2H), 1.93-2.07 (m, 2H), 1.78-1.93 (m,2H), 1.49 (s, 9H). MS (ESI) 392 (M-56+H).

Example 268 Preparation of isopropyl4-(5-chloro-1-(4-cyano-3-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Example 268 was prepared according to procedures described in Example 2substituting tert-butyl4-(5-chloro-1-(4-cyano-3-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatefor tert-butyl4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylatein Step A and substituting isopropyl chloroformate for1,1,1-trifluoropropan-2-yl chloroformate in Step C except that the crudeproduct was purified by flash chromatography (SiO₂, 0 to 100% EtOAc inCH₂Cl₂). ¹H NMR (400 MHz, CDCl₃) δ ppm 7.67-7.87 (m, 1H), 7.30-7.49 (m,3H), 6.00 (s, 1H), 4.86-5.11 (m, 1H), 4.53-4.70 (m, 1H), 3.44-3.76 (m,4H), 1.79-2.15 (m, 4H), 1.26 (s, 6H). MS (ESI) 434 (M+H).

Example 269 Preparation of4-(1-(5-ethoxypyrazin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one,TFA salt

A mixture of1-(4-(methylsulfonyl)phenyl)-4-(piperidin-4-yloxy)pyridin-2(1H)-one, HCl(39.5 mg, 0.113 mmol), 2-bromo-5-ethoxypyrazine (23 mg, 0.113 mmol), andpotassium carbonate (20.39 mg, 0.340 mmol) in DMSO (0.2 mL) was heatedin a 180° C. oil bath for 1.5 hours. The reaction mixture was added to 2mL EtOAc and washed with 3×2 mL of water, dried EtOAc over MgSO₄,filtered and concentrated to 6 mg of an amber oil. This material waspurified by preparative HPLC (C18, 50-90% MeOH in water containing 0.1%TFA) to give Example 269 (2.3 mg, 0.003 mmol, 3%) as a brown oil. MS(ESI) 471.2 (M+1).

Example 270 Preparation of tert-butyl4-(1-(4-cyano-3-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Step A. Preparation of tert-butyl4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

To 4-hydroxypyridin-2(1H)-one (11.11 g, 100 mmol) and tert-butyl4-(methylsulfonyloxy)piperidine-1-carboxylate (27.9 g, 100 mmol) in a100 mL round bottom flask was applied vacuum 5 minutes, vented tonitrogen, added DMSO (100 mL), and then added potassium carbonate (13.20g, 220 mmol). Placed in a 90° C. oil bath under nitrogen for 4.5 hours.The reaction mixture was added to 1000 mL water and 1000 mL EtOAc, thenwashed EtOAc with additional water (4×500 mL), dried with MgSO₄,filtered and concentrated to 27.3 g oily white solids. This material wasslurried 200 mL refluxing EtOAc, allowed to cool to rt, filtered, andwashed with 2×50 mL EtOAc then 2×50 mL of hexane to give product (4.86g, 16.5 mmol, 17%) as a white crystalline powder. MS (ESI) 239.1(M+1-56, indicating loss of t-butyl group the Boc group in the MS).

Step B. Preparation of tert-butyl4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

To tert-butyl4-(2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (294 mg, 1mmol), copper(I) iodide (229 mg, 1.200 mmol), quinolin-8-ol (174 mg,1.200 mmol), and potassium carbonate (180 mg, 3.00 mmol) added DMSO (5mL), bubbled nitrogen subsurface for 20 seconds, capped under nitrogenand let stir at rt for 20 minutes then added 2-fluoro-4-iodobenzonitrile(296 mg, 1.200 mmol), bubbled nitrogen subsurface 20 seconds, cappedunder nitrogen and placed in a 90° C. oil bath for 60 minutes. Thereaction mixture was added to 50 mL EtOAc+25 mL water and then filteredto remove solids and break the emulsion. The lower aqueous layer wasremoved and washed the green EtOAc layer with an additional 4×25 mL ofwater, dried with MgSO₄, filtered and concentrated to 419 mg of a lightgreen oil. This material was purified by flash chromatography (0-1% MeOHin CH₂Cl₂) to provide Example 270 (28 mg, 0.067 mmol, 7%) as a paleyellow solid. ¹H NMR (500 MHz, CDCl₃) δ ppm 1.48 (s, 9H) 1.72-1.84 (m,2H) 1.92-2.03 (m, 2H) 3.28-3.38 (m, 2H) 3.72 (br. s., 2H) 4.49 (br. s.,1H) 5.95 (br. s., 1H) 6.06 (d, J=7.70 Hz, 1H) 7.21 (d, J=7.70 Hz, 1H)7.33 (d, J=8.25 Hz, 1H) 7.38 (d, J=9.35 Hz, 1H) 7.75 (t, J=7.70 Hz, 1H).MS (ESI) 414.2 (M+1).

Example 271 Preparation of3-fluoro-4-(2-oxo-4-(1-(5-(3,3,3-trifluoropropyl)pyrimidin-2-yl)piperidin-4-yloxy)pyridin-1(2H)-yl)benzonitrile,TFA salt

Step A. Preparation of4-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-3-fluorobenzonitrile

To 4-(benzyloxy)pyridin-2(1H)-one (0.358 g, 1.779 mmol) under nitrogenwas added DMF (5 mL) to produce a tan suspension. To the reaction wasadded NaH (60% in oil) (0.074 g, 1.860 mmol) and stirred for 1.5 hoursand then 3,4-difluorobenzonitrile (0.225 g, 1.618 mmol) was added. Thereaction was placed in a 90° C. oil bath for 2 hours. To the tansuspension was added 50 mL of EtOAc and the mixture washed with 4×25 mLof water, dried over MgSO₄, filtered and concentrated to give 0.42 gpale yellow solids. This material was purified by flash chromatography(1-5% MeOH in CH₂Cl₂) to yield product (263 mg, 0.805 mmol, 50%) as atan solid. MS (ESI) 321.2 (M+1).

Step B. Preparation of3-fluoro-4-(4-hydroxy-2-oxopyridin-1(2H)-yl)benzonitrile

To 4-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-3-fluorobenzonitrile (250 mg,0.780 mmol) and 10% palladium on carbon (50 mg, 0.470 mmol) was appliedvacuum then placed under an atmosphere of nitrogen. Methanol (5 mL)wasadded and vacuum applied briefly. The reaction was placed under anatmosphere of hydrogen for 6 hours. The reaction mixture was passedthrough a 10×10 mm CELITE® 545 filter aid plug eluting with anadditional 10 mL each of MeOH and CH₂Cl₂. The filtrate was concentratedto 170 mg of a pale tan foam. Added 5 mL MeOH and heated to reflux,filtered hot and rinsed with 3×2 mL warm MeOH. The filtrate wasconcentrated to crude product (166 mg, 0.577 mmol, 74%) as a pale yellowsolid which was used as obtained in the subsequent step. MS (ESI) 231.1(M+1).

Step C Preparation of Example 271

3-Fluoro-4-(4-hydroxy-2-oxopyridin-1(2H)-yl)benzonitrile (46.0 mg, 0.2mmol), 1-(5-(3,3,3-trifluoropropyl)pyrimidin-2-yl)piperidin-4-ylmethanesulfonate (70.7 mg, 0.200 mmol), and potassium carbonate (36.0mg, 0.600 mmol) in DMF (1 mL) was placed in a 90° C. oil bath for 15hours. The reaction mixture was added to 5 mL each of EtOAc and water.The layers were separated and the organic layer was washed with 2 mL ofadditional water. Back-extracted the first aqueous with 5 mL of EtOAc,combined EtOAc solutions, then washed with a third water volume (2 mL).Dried EtOAc with MgSO₄, filtered and concentrated to 43 mg. Thismaterial was purified by preparative HPLC (C18, 50-90% MeOH in watercontaining 0.1% TFA) to give Example 271 (23 mg, 0.003 mmol, 3%) as apale yellow foam. ¹H NMR (500 MHz, CDCl₃) δ ppm 2.07 (d, J=4.40 Hz, 2H)2.11-2.28 (m, 2H) 2.31-2.54 (m, 2 H) 2.86 (t, J=7.70 Hz, 2H) 3.79-4.18(m, 4H) 4.75 (br. s., 1H) 6.25 (d, J=7.70 Hz, 1H) 6.45 (br. s., 1H) 7.23(d, J=7.70 Hz, 1H) 7.48-7.70 (m, 3H) 8.49 (s, 2H). MS (ESI) 488.2 (M+1).

Example 272 Preparation of4-(1-(5-methoxypyrazin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one,TFA salt

Example 272 was prepared using the procedure described for Example 269and substituting 2-bromo-5-methoxypyrazine for 2-bromo-5-ethoxypyrazine.MS (ESI) 457.3 (M+1).

Example 273 Preparation of4-(1-(5-chloropyrazin-2-yl)piperidin-4-yloxy)-1-(4-(methylsulfonyl)phenyl)pyridin-2(1H)-one,TFA salt

Example 273 was isolated from the reaction mixture used to produceExample 272 and resulted from the impurity 2-chloro-5-methoxypyrazinecontained within the reagent 2-bromo-5-methoxypyrazine. MS (ESI) 461.1(M+1).

Example 274 Preparation of4-(4-(1-(5-cyclobutylpyrimidin-2-yl)piperidin-4-yloxy)-2-oxopyridin-1(2H)-yl)-3-fluorobenzonitrile

To a mixture of 3-fluoro-4-(4-hydroxy-2-oxopyridin-1(2H)-yl)benzonitrile(46.0 mg, 0.2 mmol), 1-(5-cyclobutylpyrimidin-2-yl)piperidin-4-ylmethanesulfonate (62.3 mg, 0.200 mmol), and potassium carbonate (36.0mg, 0.600 mmol) was added DMF (1 mL), capped and placed in a 90° C. oilbath for 110 minutes. The reaction mixture was added to 5 mL EtOAc plus5 mL water, backwashed water layer with 2×2 mL EtOAc then washedcombined EtOAc solutions with 2×2 mL water. Dried EtOAc with MgSO₄,filtered, and concentrated to 71 mg of a pale yellow solid. Thismaterial was purified by preparative HPLC (C18, 50-90% MeOH in watercontaining 0.1% TFA) to give Example 274 (42 mg, 0.074 mmol, 37%) as anoff-white foam. ¹H NMR (500 MHz, CDCl₃) δ ppm 1.86-2.01 (m, 1H)2.01-2.23 (m, 6H) 2.32-2.50 (m, 2H) 3.39-3.57 (m, 1H) 4.07 (br. s., 3H)4.73 (br. s., 1H) 6.21 (d, J=7.70 Hz, 1 H) 6.34 (br. s., 1H) 7.21 (d,J=7.70 Hz, 1H) 7.48-7.69 (m, 3H) 8.45 (s, 2H). MS (ESI) 446.3 (M+1).

Assays for GPR119 G Protein-Coupled Receptor Activity

The in vitro modulation of recombinant human GPR119 was determined asfollows.

HIT-T15 cAMP Assay

A HIT-T15 hamster insulinoma cell line was purchased from ATCC and grownin the medium recommended by ATCC (i.e., Growth Medium: F12K Medium(Invitrogen 21127-022; 10% D-horse Serum; and 2.5% FBS).

To conduct the cAMP assay, cells expressing a GPR119 receptor are platedon 96 well plates (e.g., BD Falcon: REF 353948, black side, clearbottom, TC surface) at a density of about 4.5×10⁴ cells per well ingrowth medium and incubated overnight. Following incubation, the growthmedium is removed from the wells followed by a single rinse with theassay buffer from the Hit Hunter cAMP kit (100 μl/well). Following therinse, 20 μl of assay buffer is added to each well followed by additionof 10 μl of a 3× concentration of compound working solution. Thesolution is then mixed well. The final concentration range of compoundis from about 10⁻⁵M to about 10⁻¹¹M. The reaction is incubated at 37°C., in a 5% CO₂ for 1 hour. Following incubation, the cAMP concentrationis determined using the Hit Hunter cAMP kit according to themanufacturer's protocol.

Human Tet-inducible cAMP Assay

Cell lines expressing GPR119 are generated using the Flp-In-T-REx 293tetracycline inducible gene expression system are cultured in culturemedium comprising the following components: DMEM#11965, 10% FBS, 2 mML-glutamine, 200 ug/ml Hygromycin B, and 15 ug/ml blasticidin.

For cAMP assays, cells are plated on 96 well plates (e.g., BD Falcon:REF 353948, black side, clear bottom, TC surface) at a density of about4.5×10⁴ cells per well in growth medium containing LOug/ml tetracycline(1.0 mg/ml stock). The cells are then incubated for 48 hours at 37° C.

Following the incubation, the growth medium is removed from the wellsand the wells rinsed (once) with the assay buffer included in the HitHunter cAMP kit (100 μl/well). Following the wash, 20 μl of assay bufferis added to each well, followed by addition of 10 μl of a 3×concentration compound working solution. The solution is then mixed. Thefinal concentration range of compound is from about 10⁻⁵M to about10⁻¹¹M. The reagents are then incubated at 37° C. at 5% CO₂ for 1 hour.

The manufacturer's protocol may be followed for cAMP determination. TheHit Hunter cAMP kit protocol is outlined for the HIT-T15 cAMP assaysdescribed above.

Compounds of the present invention were tested in the HumanTet-inducible cAMP assay described immediately above and the resultsshown in Table 1 below were obtained.

TABLE 1 Example hGPR119 EC₅₀ (nM) 12 3489 27 3502 51 314 74 275 78 30382 4027 83 4340 84 3274 86 3519 91 304 108 261 125 293 133 250 143 274153 273 162 5000 165 5000 175 8 177 8 178 265 179 276 184 5000 189 7143191 5088 192 241 194 5 199 7 202 2 206 293 207 7075 209 3388 224 6 227 1229 4 239 9 243 9 261 257 263 4 265 4 267 4

Luciferase Assay

HEK 293 cells may be plated on poly-D-lysine treated 96-well BD blackside/clear bottom plates at a density of about 3×10⁴ cells/well ingrowth medium. The growth medium may comprise the following: D-MEM (Cat#12430) with high glucose and 10% fetal bovine serum.

Cells may be transfected with vectors comprising native or non-nativeGPR119 sequences using commercially available vectors (e.g., Stratagene)and transfection reagents. The standard manufacturer's protocols may befollowed to transfect the cells. Following transfection, thetransfection medium may be removed and assay medium added to the wellsof the assay plates.

Once the assay plates are prepared, compound dilution plates may bemade. To do so, make a first compound dilution plate using 10 mM of thecompound of interest diluted to about 1 mM in DMSO. Then make 12 pointhalf-log dilutions of the compounds (in DMSO) using an automated liquidhandler. Next, make a second dilution plate by diluting the wells in thefirst plate ten fold (10×) using assay medium. Once the plates arecomplete, the highest dose is about 10 μM and the lowest dose is about0.03 nM.

Once the dilution plates are complete, one can add about 10 μl of the10× compound dilution to the assay plate containing the assay mediumtransiently transfected cells. Tap the plate to mix the reagents andincubate the plate overnight at 37° C., 95% O₂, and 5% CO₂ in anincubator.

Following incubation, a luciferase assay system may be used (e.g.,Stead-Glo Luciferase Assay System from Promega) according to themanufacturer's instructions. Following completion of the reaction,immediately measure the readout of the assay using a top countluminometer.

Mouse Oral Glucose Tolerance Test

24 male C57BL/6J mice (8-10 weeks old, average weight 28 g) wererandomized into 4 groups (1 mouse/cage) of 6 mice per group based on fedplasma glucose and body weight. Prior to initiating the study, mice werefasted overnight and the next morning they were weighed and placed inthe experimental lab. After 30 min in the environment, the mice werebled via tail tip at −30 min and immediately given their first oraladministration of vehicle (0.5% Methocel, 0.1% Tween 80 in water) orcompound solutions (5 ml/kg). At time 0 the mice were bled and given 50%glucose (2 g/kg) to initiate the oral glucose tolerance test (oGTT). Themice were bled 30, 60 and 120 min after the glucose load. Blood sampleswere drawn into potassium EDTA, placed on ice during the study andsubsequently centrifuged for 10 min at 3000 rpm at 4° C. Plasma sampleswere diluted 11-fold for glucose analysis in the Cobas Mira System(Roche Diagnostics). Area under the curve was calculated from the plasmaglucose time course data using the trapezoid rule with fasting plasmaglucose as the baseline (GraphPad Prism Software). The statisticalsignificance of the changes in the glucose AUCs resulting from thedifferent treatments was determined by one-way ANOVA followed byDunnett's test using the vehicle group as the control (JMP software,release 5.1.2).

TABLE 2 Example Glucose Lowering (%) 3 −29

Utilities and Combinations A. Utilities

The compounds of the present invention possess activity as agonists ofthe GPR119 receptor, and, therefore, may be used in the treatment ofdiseases associated with GPR119 receptor activity. Via the activation ofGPR119 receptor, the compounds of the present invention may preferablybe employed to increase insulin production or increase GLP-1 secretionor both.

Accordingly, the compounds of the present invention can be administeredto mammals, preferably humans, for the treatment of a variety ofconditions and disorders, including, but not limited to, treating,preventing, or slowing the progression of diabetes and relatedconditions, microvascular complications associated with diabetes,macrovascular complications associated with diabetes, cardiovasculardiseases, Metabolic Syndrome and its component conditions, inflammatorydiseases and other maladies. Consequently, it is believed that thecompounds of the present invention may be used in preventing,inhibiting, or treating diabetes, hyperglycemia, impaired glucosetolerance, insulin resistance, hyperinsulinemia, retinopathy,neuropathy, nephropathy, wound healing, atherosclerosis and its sequelae(acute coronary syndrome, myocardial infarction, angina pectoris,peripheral vascular disease, intermittent claudication, myocardialischemia, stroke, heart failure), Metabolic Syndrome, hypertension,obesity, dyslipidemia, hyperlipidemia, hypertriglyceridemia,hypercholesterolemia, low HDL, high LDL, vascular restenosis, peripheralarterial disease, lipid disorders, bone disease (includingosteoporosis), PCOS, HIV protease associated lipodystrophy, glaucoma andinflammatory diseases, such as, psoriasis, rheumatoid arthritis andosteoarthritis, and treatment of side-effects related to diabetes,lipodystrophy and osteoporosis from corticosteroid treatment.

Metabolic Syndrome or “Syndrome X” is described in Ford et al., J. Am.Med. Assoc., 287:356-359 (2002) and Arbeeny et al., Curr. Med.Chem.—Imm., Endoc. & Metab. Agents, 1:1-24 (2001).

B. Combinations

The present invention includes within its scope pharmaceuticalcompositions comprising, as an active ingredient, a therapeuticallyeffective amount of at least one of the compounds of Formula I and IA,alone or in combination with a pharmaceutical carrier or diluent.Optionally, compounds of the present invention can be used alone, incombination with other compounds of the invention, or in combinationwith one or more other therapeutic agent(s), e.g., an antidiabetic agentor other pharmaceutically active material.

The compounds of the present invention may be employed in combinationwith other GPR119 receptor agonists or one or more other suitabletherapeutic agents useful in the treatment of the aforementioneddisorders including: anti-diabetic agents, anti-hyperglycemic agents,anti-hyperinsulinemic agents, anti-retinopathic agents, anti-neuropathicagents, anti-nephropathic agents, anti-atherosclerotic agents,anti-ischemic agents, anti-hypertensive agents, anti-obesity agents,anti-dyslipidemic agents, anti-dyslipidemic agents, anti-hyperlipidemicagents, anti-hypertriglyceridemic agents, anti-hypercholesterolemicagents, anti-restenotic agents, anti-pancreatic agents, lipid loweringagents, appetite suppressants, treatments for heart failure, treatmentsfor peripheral arterial disease and anti-inflammatory agents.

Examples of suitable anti-diabetic agents for use in combination withthe compounds of the present invention include insulin and insulinanalogs (e.g., LysPro insulin, inhaled formulations comprising insulin);glucagon-like peptides; sulfonylureas and analogs (e.g., chlorpropamide,glibenclamide, tolbutamide, tolazamide, acetohexamide, glypizide,glyburide, glimepiride, repaglinide, meglitinide); biguanides (e.g.,metformin, phenformin, buformin); alpha2-antagonists and imidazolines(e.g., midaglizole, isaglidole, deriglidole, idazoxan, efaroxan,fluparoxan); other insulin secretagogues (e.g., linogliride,insulinotropin, exendin-4,N,N-dimethyl-N′-[2-(4-morpholinyl)phenyl]guanidine (E)-2-butenedioatesalt (BTS-675820),(−)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166));thiazolidinediones and PPAR-gamma agonists (e.g., ciglitazone,pioglitazone, troglitazone, rosiglitazone); PPAR-alpha agonists e.g.,fenofibrate, gemfibrozil); PPAR alpha/gamma dual agonists (e.g.,muraglitazar, peliglitazar); SGLT2 inhibitors (e.g.,3-(Benzo[b]furan-5-yl)-2′,6′-dihydroxy-4′-methylpropiophenone-2′-O-(6-O-methoxycarbonyl)-β-d-glucopyranoside(T-1095 Tanabe Seiyaku), phlorizin, TS-033 (Taisho), dapagliflozin(BMS), sergiflozin (Kissei), AVE 2268 (Sanofi-Aventis));11-beta-hydroxysteriod dehydrogenase type I inhibitors (e.g., AMG221,INCB13739); dipeptidyl peptidase-IV (DPP4) inhibitors (e.g.,saxagliptin, sitagliptin, vildagliptin, and denagliptin); glucagon-likepeptide-1 (GLP-1) receptor agonists (e.g., Exenatide (Byetta™), NN2211(Liraglutide, Novo Nordisk), AVE0010 (Sanofi-Aventis), R1583(Roche/Ipsen), SUN E7001 (Daiichi/Santory), GSK-716155 (GSK/Human GenomeSciences) and Exendin-4 (PC-DAC™); aldose reductase inhibitors (e.g.,those disclosed in WO 99/26659); RXR agonists (e.g., reglitizar(JTT-501),5-[[6-[(2-fluorophenyl)methoxy]-2-naphthalenyl]methyl]-2,4-Thiazolidinedione(MCC-555),5-[[3-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)-4-(trifluoromethoxy)phenyl]methylene]-2,4-Thiazolidinedione(MX-6054), DRF2593, farglitazar,(±)-5-[(2,4-dioxothiazolidin-5-yl)methyl]-2-methoxy-N-[[(4-trifluoromethyl)phenyl]methyl]benzamide(KRP-297),6-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)cyclopropyl]-3-Pyridinecarboxylicacid (LG100268)); fatty acid oxidation inhibitors (e.g., clomoxir,etomoxir; α-glucosidase inhibitors: precose, acarbose, miglitol,emiglitate, voglibose,2,6-dideoxy-2,6-imino-7-O-β-D-glucopyranosyl-D-glycero-L-gulo-heptitol(MDL-25,637), camiglibose); beta-agonists (e.g., Methyl ester[4-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]-Aceticacid (BRL 35135),2-[4-[(2S)-2-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]-Aceticacid (BRL 37344),4-[(3R)-3-[bis[(2R)-2-hydroxy-2-phenylethyl]amino]butyl]-Benzamide (Ro16-8714),2-[4-[2-[[(2S)-2-hydroxy-3-phenoxypropyl]amino]ethoxy]phenoxy]-N-(2-methoxyethyl)-Acetamide(ICI D7114),5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-3-Benzodioxole-2,2-dicarboxylicacid, disodium salt (CL 316,243), TAK-667, AZ40140); phosphodiesteraseinhibitors, both cAMP and cGMP type (e.g., sildenafil,9-((1S,2R)-2-fluoro-1-methylpropyl)-2-methoxy-6-(1-piperazinyl)purinehydrochloride (L-686398), L-386,398); amylin agonists (e.g.,pramlintide); lipoxygenase inhibitors (e.g., masoprocal); somatostatinanalogs (e.g., lanreotide, seglitide, octreotide); glucagon antagonists(e.g., BAY 276-9955); insulin signaling agonists, insulin mimetics,PTP1B inhibitors (e.g.,2-[2-(1,1-dimethyl-2-propenyl)-1H-indol-3-yl]-3,6-dihydroxy-5-[7-(3-methyl-2-butenyl)-1H-indol-3-yl]-2,5-Cyclohexadiene-1,4-dione(L-783281), TER17411, TER17529); gluconeogenesis inhibitors (e.g.,GP3034); somatostatin analogs and antagonists; antilipolytic agents(e.g., nicotinic acid, acipimox, N-cyclohexyl-2′-O-methyl-Adenosine (WAG994)); glucose transport stimulating agents (e.g.,4-chloro-α-[(4-methylphenyl)sulfonyl]-benzeneheptanoic acid(BM-130795)); glucose synthase kinase inhibitors (e.g., lithiumchloride, CT98014, CT98023); galanin receptor agonists; Chemokinereceptor antagonist CCR2/5 (e.g., NCB3284, MK-0812, INCB8696, maraviroc(Pfizer) and vicriviroc); thyroid receptor agonists (e.g., KB-2115(KaroBio)); Glucokinase activators (e.g., RO-27-4375, RO-28-1675(Roche),6-[[3-[(1S)-2-methoxy-1-methylethoxy]-5-[(1S)-1-methyl-2-phenylethoxy]benzoyl]amino]-3-Pyridinecarboxylicacid (GKA-50 AstraZeneca)); GPR119 agonists (e.g., 1,1-dimethylethylester4-[[3-(4-pyridinyl)-1,2,4-oxadiazol-5-yl]methoxy]-1-Piperidinecarboxylicacid (PSN-632408 OSI Prosidion)); GDIR agonists (e.g., APD668 (Arena));GPR40 modulators(e.g.,(S)-4-(dimethylamino)-3-(4-((4-methyl-2-p-tolylthiazol-5-yl)methoxy)phenyl)-4-oxobutanoicacid,6-chloro-2-(4-chlorobenzylthio)-1-(4-(methoxymethoxy)phenyl)-1H-benzo[d]imidazole).

Examples of suitable lipid lowering agents and anti-atheroscleroticagents for use in combination with the compounds of the presentinvention include one or more MTP/ApoB secretion inhibitors (e.g.,dirlopatide,N-(2,2,2-Trifluoroethyl)-9-[4-[4-[[[4′-(trifluoromethyl)[1,1′-biphenyl]-2-yl]carbonyl-]amino]-1-piperidinyl]butyl]-9H-fluorene-9-carboxamide,methanesulfonate, CP-741952 (Pfizer), SLx-4090 (Surface Logix)); HMG CoAreductase inhibitors (e.g., atorvastatin, rosuvastatin, simvastatin,pravastatin, lovastatin, fluvastatin); squalene synthetase inhibitors,PPAR alpha agonists and fabric acid derivatives (e.g., fenofibrate,gemfibrozil); ACAT inhibitors; lipoxygenase inhibitors; cholesterolabsorption inhibitors (e.g., ezetimibe); thyroid receptor agonists(e.g., as set forth above); Ileal Na⁺/bile acid cotransporter inhibitors(e.g., compounds as disclosed in Drugs of the Future, 24:425-430 (1999);upregulators of LDL receptor activity (e.g.,(3R)-3-[(13R)-β-hydroxy-10-oxotetradecyl]-5,7-dimethoxy-1(3H)-Isobenzofuranone(Taisho Pharmaceutical Co. Ltd) and(3α,4α,5α)-4-(2-propenyl)-Cholestan-3-ol (Eli Lilly); bile acidsequestrants (e.g., WELCHOL®, COLESTID®, LOCHOLEST® and QUESTRAN®; andfabric acid derivatives, such as ATROMID®, LOPID® and TRICOT®);cholesterol ester transfer protein inhibitors (e.g., torcetrapib and(2R)-3-{[3-(4-chloro-3-ethyl-phenoxy)-phenyl]-[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino}-1,1,1-trifluoro-2-propanol);nicotinic acid and derivatives thereof (e.g., niacin, acipimox); PCSK9inhibitors; LXR agonists (e.g., those disclosed in U.S. PatentApplication Publication Nos. 2003/01814206, 2005/0080111, and2005/0245515); lipoxygenase inhibitors (e.g., such as benzimidazolederivatives, as disclosed in WO 97/12615, 15-LO inhibitors, as disclosedin WO 97/12613, isothiazolones, as disclosed in WO 96/38144, and 15-LOinhibitors, as disclosed by Sendobry et al., “Attenuation ofdiet-induced atherosclerosis in rabbits with a highly selective15-lipoxygenase inhibitor lacking significant antioxidant properties”,Brit. J. Pharmacology, 120:1199-1206 (1997), and Cornicelli et al.,“15-Lipoxygenase and its Inhibition: A Novel Therapeutic Target forVascular Disease”, Current Pharmaceutical Design, 5:11-20 (1999)).

Preferred hypolipidemic agents are pravastatin, lovastatin, simvastatin,atorvastatin, fluvastatin, cerivastatin, atavastatin, and rosuvastatin.

Examples of suitable anti-hypertensive agents for use in combinationwith the compounds of the present invention include beta adrenergicblockers, calcium channel blockers (L-type and T-type; e.g., diltiazem,verapamil, nifedipine, amlodipine and mybefradil), diuretics (e.g.,chlorothiazide, hydrochlorothiazide, flumethiazide, hydroflumethiazide,bendroflumethiazide, methylchlorothiazide, trichloromethiazide,polythiazide, benzthiazide, ethacrynic acid tricrynafen, chlorthalidone,furosemide, musolimine, bumetanide, triamtrenene, amiloride,spironolactone), renin inhibitors (e.g., aliskiren), ACE inhibitors(e.g., captopril, zofenopril, fosinopril, enalapril, ceranopril,cilazopril, delapril, pentopril, quinapril, ramipril, lisinopril), AT-1receptor antagonists (e.g., losartan, irbesartan, valsartan), ETreceptor antagonists (e.g., sitaxsentan, atrsentan, and compoundsdisclosed in U.S. Pat. Nos. 5,612,359 and 6,043,265), Dual ET/AIIantagonist (e.g., compounds disclosed in WO 00/01389), neutralendopeptidase (NEP) inhibitors, vasopeptidase inhibitors (dual NEP-ACEinhibitors) (e.g., omapatrilat and gemopatrilat), nitrates, centralalpha agonists (e.g., clonidine), alpha1 blockers (e.g., prazosine),arterial vasodilators (e.g., minoxidil), sympatolytics (e.g.,resperine), renin inhibitors (e.g., Aliskiren (Novartis)).

Examples of suitable anti-obesity agents for use in combination with thecompounds of the present invention include a cannabinoid receptor 1antagonist or inverse agonist (e.g., rimonabant,(4S)-3-(4-chlorophenyl)-N-[(4-chlorophenyl)sulfonyl]-4,5-dihydro-N′-methyl-4-phenyl-1H-Pyrazole-1-carboximidamide(SLV 319), CP-945598 (Pfizer), Surinabant (SR-147778, Sanofi-Aventis),N-[(1S,2S)-3-(4-Chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-{[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide(Merck) and those discussed in Hertzog, D. L., Expert Opin. Ther.Patents, 14:1435-1452 (2004)); a beta 3 adrenergic agonist (e.g.,rafabegron (AJ9677, Takeda/Dainippon),N-[4-[2-[[(2S)-3-[(6-amino-3-pyridinyl)oxy]-2-hydroxypropyl]amino]ethyl]phenyl]-4-(1-methylethyl)-Benzenesulfonamide(L750355, Merck), or CP331648 (Pfizer,) or other known beta 3 agonists,as disclosed in U.S. Pat. Nos. 5,541,204, 5,770,615, 5,491,134,5,776,983, and 5,488,064, with rafabegron,N-[4-[2-[[(2S)-3-[(6-amino-3-pyridinyl)oxy]-2-hydroxypropyl]amino]ethyl]phenyl]-4-(1-methylethyl)-benzenesulfonamide,and CP331648 being preferred); a lipase inhibitor (e.g., orlistat orcetilistat, with orlistat being preferred); a serotonin andnorepinephrine reuptake inhibitor (e.g., sibutramine, Abbott andtesofensine, Neurosearch) with sibutramine being preferred; a dopaminereuptake inhibitor (e.g., buproprion, GSK); or 5-HT_(2C) agonist, (e.g.,lorcaserin hydrochloride (Arena), WAY-163909[(7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole]:with lorcaserin hydrochloride being preferred); 5-HT6 receptorantagonists (Suven, Biovitrum, Epix), anti-epileptics topiramate(Johnson & Johnson) and zonisamide, a ciliary neurotrophic factoragonist (e.g., axokine (Regeneron); brain-derived neurotrophic factor(BDNF), orexin antagonists, histamine receptor-3 (H3) modulators,melanin-concentrating hormone receptor (MCHR) antagonists (e.g.,GSK-856464 (GlaxoSmithKline), T-0910792 (Amgen)); diacylglycerolacyltransferase (DGAT) inhibitors (e.g., BAY-74-4113 (Bayer));acetyl-CoA carboxylase (ACC) inhibitors (e.g.,N-(4-(4-(4-isopropoxyphenoxy)phenyl)but-3-yn-2-yl)acetamide (A-80040,Abbott),(R)-anthracen-9-yl(3-(morpholine-4-carbonyl)-1,4′-bipiperidin-1′-yl)methanone(CP-640186, Pfizer)), SCD-1 inhibitors as described by Jiang et al.,Diabetes (2004) 53, (abs 653-p); amylin receptor agonists (e.g.,compounds disclosed in WO 2005/025504); thyroid receptor agonists (e.g.,as set forth above); growth hormone secretagogue receptor (GHSR)antagonists (e.g., A-778193 (Abbott), leptin and leptin mimetics (e.g.,OB-3 (Aegis/Albany Medical College), leptin analogs A-100 and A-200(Amgen), CBT-001452 (Cambridge Biotechnology), ML-22952 (Millennium)),PYY receptor agonist (e.g., AC-162352 (Amylin), PYY-3-36 (Emishere),PYY(3-36)NH₂ (Unigene)), NPY-Y4 agonists (7™ Pharma WO2005/089786(A2,A3)-1), NPY-5 antagonists (e.g., NPYSRA-972(AstraZeneca), GW-594884A (GlaxoSmithKline), J-104870 (Banyu)); MTP/apoBsecretion inhibitors (as set forth above), and/or an anorectic agent.

The anorectic agent which may be optionally employed in combination withcompounds of the present invention include dexamphetamine, phentermine,phenylpropanolamine, or mazindol, with dexamphetamine being preferred.

Other compounds that can be used in combination with the compounds ofthe present invention include CCK receptor agonists (e.g., SR-27895B);galanin receptor antagonists; MCR-4 antagonists (e.g.,N-acetyl-L-norleucyl-L-glutaminyl-L-histidyl-D-phenylalanyl-L-arginyl-D-tryptophyl-Glycinamide,(HP-228); urocortin mimetics, CRF antagonists, and CRF binding proteins(e.g., mifepristone (RU-486), urocortin).

Further, the compounds of the present invention may be used incombination with HIV protease inhibitors, including but not limited toReyataz® and Kaletra®.

Examples of suitable memory enhancing agents, anti-dementia agents, orcognition promoting agents for use in combination with the compounds ofthe present invention include, but are not limited to aricept, razadyne,donepezil, rivastigmine, galantamine, memantine, tacrine, metrifonate,muscarine, xanomelline, deprenyl and physostigmine

Examples of suitable anti-inflammatory agents for use in combinationwith the compounds of the present invention include, but are not limitedto, NSAIDS, prednisone, acetaminophen, aspirin, codeine, fentanyl,ibuprofen, indomethacin, ketorolac, morphine, naproxen, phenacetin,piroxicam, sufentanyl, sunlindac, interferon alpha, prednisolone,methylprednisolone, dexamethazone, flucatisone, betamethasone,hydrocortisone, beclomethasone, remicade, orencia, and enbrel.

The aforementioned patents and patent applications are incorporatedherein by reference.

The above other therapeutic agents, when employed in combination withthe compounds of the present invention may be used, for example, inthose amounts indicated in the Physicians' Desk Reference, as in thepatents set out above, or as otherwise determined by one of ordinaryskill in the art.

The compounds of Formula I and IA can be administered for any of theuses described herein by any suitable means, for example, orally, suchas in the form of tablets, capsules, granules or powders; sublingually;bucally; parenterally, such as by subcutaneous, intravenous,intramuscular, or intrasternal injection, or infusion techniques (e.g.,as sterile injectable aqueous or non-aqueous solutions or suspensions);nasally, including administration to the nasal membranes, such as byinhalation spray; topically, such as in the form of a cream or ointment;or rectally such as in the form of suppositories; in dosage unitformulations containing non-toxic, pharmaceutically acceptable vehiclesor diluents.

In carrying out the method of the invention for treating diabetes andrelated diseases, a pharmaceutical composition will be employedcontaining the compounds of Formula I and/or IA, with or without otherantidiabetic agent(s) and/or antihyperlipidemic agent(s) and/or othertype therapeutic agents in association with a pharmaceutical vehicle ordiluent. The pharmaceutical composition can be formulated employingconventional solid or liquid vehicles or diluents and pharmaceuticaladditives of a type appropriate to the mode of desired administration,such as pharmaceutically acceptable carriers, excipients, binders, andthe like. The compounds can be administered to a mammalian patient,including humans, monkeys, dogs, etc. by an oral route, for example, inthe form of tablets, capsules, beads, granules or powders. The dose foradults is preferably between 1 and 2,000 mg per day, which can beadministered in a single dose or in the form of individual doses from1-4 times per day.

A typical capsule for oral administration contains compounds of FormulaI and/or IA (250 mg), lactose (75 mg), and magnesium stearate (15 mg).The mixture is passed through a 60 mesh sieve and packed into a No. 1gelatin capsule.

A typical injectable preparation is produced by aseptically placing 250mg of compounds of Formula I and/or IA into a vial, asepticallyfreeze-drying and sealing. For use, the contents of the vial are mixedwith 2 mL of physiological saline, to produce an injectable preparation.

1. A compound selected from compounds of Formula I and Formula IA:

and enantiomers, diastereomers, solvates and pharmaceutically acceptablesalts thereof having ring A and ring B, wherein: ring A is optionallysubstituted with one or more R's shown as R₂₀ and R₂₁; G is CH or N; Qis C; X is N; Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂; n₁is 0-2; n₂ is 0-2; n₃ is 1-2; R₁ is a 6-membered monocyclic aryl, a5-membered monocyclic heteroaryl or a 6-membered monocyclic heteroaryl,each of which may be optionally substituted with one or more membersselected from R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e); R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e) are each independently selected from the groupconsisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl,heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₁,—OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉, —S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉,—C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) the alkenyl, alkynyl,cycloalkyl, aryl and heterocyclyl may each be optionally substitutedwith one or more R₆'s; and (b) the alkyl may optionally be substitutedby one or more of R₇'s; R₂ is cycloalkyl, aryl, heteroaryl,heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅, —C(═O)R₅ or —C(═O)OR₅, wherein thecycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionallysubstituted with one or more R₆'s; R₃ is hydrogen, alkyl, alkoxy,cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclylor heterocyclylalkyl; R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroarylor heterocyclyl, each of which may be optionally substituted with one ormore R₆'s; R₆, at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)NR₉S(O)₂R₉, —S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉,—C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—C(═NR₁₄)NR₉R₉, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl,cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-5R_(9a); R₇, at each occurrence, is independently selected from the groupconsisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a); R₈, at each occurrence, is independently selected from thegroup consisting of alkyl, aryl, cycloalkyl, heteroaryl andheterocyclyl, each of which may be optionally substituted with one ormore R_(8a)'s; R_(8a), at each occurrence, is independently selectedfrom alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄; R₉, at eachoccurrence, is independently selected from hydrogen, alkyl, alkoxy,cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyland heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may eachbe optionally substituted with 0-5 R_(9a); R_(9a), at each occurrence,is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₁, ateach occurrence, is independently selected from alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(11a); R_(10a) at eachoccurrence, is independently selected from alkyl, haloalkyl, aryl,alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉, —S(O)₂NR₁₄C(═O)NR₁₄R₁₄,—C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄,—C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₂, at each occurrence, isindependently selected from hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(10a); R₁₄, at eachoccurrence, is independently selected from hydrogen, alkyl, cycloalkyland aryl; and R₂₀ and R₂₁ are each independently selected from the groupconsisting of hydrogen, alkyl, haloalkyl, cycloalkyl, phenyl, halo, —CN,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and—OC(═O)R₁₀.
 2. A compound according to claim 1 selected from the groupconsisting of compounds of Formula I and IA wherein: ring A isoptionally substituted with one or more R's shown as R₂₀ and R₂₁; G isCH or N; Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂; n₁ is0-2; n₂ is 0-2; n₃ is 1-2; R₁ is phenyl, pyridinyl, pyrazinyl orpyrimindinyl, each of which may be optionally substituted with one ormore members selected from R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e);R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s; R₂ is cycloalkyl,aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅, —C(═O)R₅ or—C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; R₃ is hydrogen,alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl or heterocyclylalkyl; R₅ is alkyl, alkenyl, aryl,cycloalkyl, heteroaryl or heterocyclyl, each of which may be optionallysubstituted with one or more R₆'s; R₆, at each occurrence, isindependently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₀, —OCF₃,—OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₉R₉, —NR₉R₉,—S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉, —S(O)₂NR₉C(═O)OR₉,—S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H,—NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀,—S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl,alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl may each be optionally substitutedwith 0-5 R_(9a); R₇, at each occurrence, is independently selected fromthe group consisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a); R₈, at each occurrence, is independently selected from thegroup consisting of alkyl, aryl, cycloalkyl, heteroaryl andheterocyclyl, each of which may be optionally substituted with one ormore R_(8a)'s; R_(8a), at each occurrence, is independently selectedfrom alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄; R₉, at eachoccurrence, is independently selected from hydrogen, alkyl, alkoxy,cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyland heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may eachbe optionally substituted with 0-5 R_(9a); R_(9a), at each occurrence,is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₁, ateach occurrence, is independently selected from alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(11a); R_(11a), at eachoccurrence, is independently selected from alkyl, haloalkyl, aryl,alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉, —S(O)₂NR₁₄C(═O)NR₁₄R₁₄,—C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄,—C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₂, at each occurrence, isindependently selected from hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(10a); R₁₄, at eachoccurrence, is independently selected from hydrogen, alkyl, cycloalkyland aryl; and R₂₀ and R₂₁ are each independently selected from the groupconsisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and—OC(═O)R₁₀.
 3. A compound according to claim 1 selected from the groupconsisting of compounds of Formula I and IA wherein: ring A isoptionally substituted with one or more R's shown as R₂₀ and R₂₁; G isCH or N; Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂; n₁ is0-2; n₂ is 0-2; n₃ is 1-2; R₁ is

each of which may be optionally substituted with one or more membersselected from the group consisting of R_(1a), R_(1b), R_(1c), R_(1d) andR_(1e); R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of VS; R₂ is cycloalkyl,aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅, —C(═O)R₅ or—C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; R₃ is hydrogen,alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl or heterocyclylalkyl, wherein the heteroaryl; R₅ is alkyl,alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, each of which maybe optionally substituted with one or more R₆'s; R₆, at each occurrence,is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₀, —OCF₃,—OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₉R₉, —NR₉R₉,—S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉, —S(O)₂NR₉C(═O)OR₉,—S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H,—NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀,—S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl,alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl may each be optionally substitutedwith 0-5 R_(9a); R₇, at each occurrence, is independently selected fromthe group consisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a); R₈, at each occurrence, is independently selected from thegroup consisting of alkyl, aryl, cycloalkyl, heteroaryl andheterocyclyl, each of which may be optionally substituted with one ormore R_(8a)'s; R_(8a), at each occurrence, is independently selectedfrom alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄; R₉, at eachoccurrence, is independently selected from hydrogen, alkyl, alkoxy,cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyland heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may eachbe optionally substituted with 0-5 R_(9a); R_(9a), at each occurrence,is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₁, ateach occurrence, is independently selected from alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(11a); R_(11a), at eachoccurrence, is independently selected from alkyl, haloalkyl, aryl,alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉, —S(O)₂NR₁₄C(═O)NR₁₄R₁₄,—C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄,—C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄; —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₂, at each occurrence, isindependently selected from hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(10a); R₁₄, at eachoccurrence, is independently selected from hydrogen, alkyl, cycloalkyland aryl; and R₂₀ and R₂₁ are each independently selected from the groupconsisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and—OC(═O)R₁₀.
 4. A compound according to claim 1 selected from the groupconsisting of compounds of Formula I and IA wherein: ring A isoptionally substituted with one or more R's shown as R₂₀ and R₂₁; G isCH or N; Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂; m is 0-2;n₂ is 0-2; n₃ is 1-2; R₁ is a 6-membered monocyclic aryl, a 5-memberedmonocyclic heteroaryl or a 6-membered monocyclic heteroaryl, each ofwhich may be optionally substituted with one or more members selectedfrom R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e); R_(1a), R_(1b), R_(1c),R_(1d) and R_(1e) are each independently selected from the groupconsisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl,heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₁,—OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉, —S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉,—C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) the alkenyl, alkynyl,cycloalkyl, aryl and heterocyclyl may each be optionally substitutedwith one or more R₆'s; and (b) the alkyl may optionally be substitutedby one or more of VS; R₂ is aryl, heteroaryl, heterocyclyl, —C(═O)NR₃R₅,—C(═O)R₅ or —C(═O)OR₅, wherein the aryl, heteroaryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; R₃ is hydrogen,alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl or heterocyclylalkyl; R₅ is alkyl, alkenyl, aryl,cycloalkyl, heteroaryl or heterocyclyl, each of which may be optionallysubstituted with one or more R₆'s; R₆, at each occurrence, isindependently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₀, —OCF₃,—OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₉R₉, —NR₉R₉,—S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉, —S(O)₂NR₉C(═O)OR₉,—S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H,—NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀,—S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl,alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl may each be optionally substitutedwith 0-5 R_(9a); R₇, at each occurrence, is independently selected fromthe group consisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a); R₈, at each occurrence, is independently selected from thegroup consisting of alkyl, aryl, cycloalkyl, heteroaryl andheterocyclyl, each of which may be optionally substituted with one ormore R_(8a)'s; R_(8a), at each occurrence, is independently selectedfrom alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄; R₉, at eachoccurrence, is independently selected from hydrogen, alkyl, alkoxy,cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyland heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may eachbe optionally substituted with 0-5 R_(9a); R_(9a), at each occurrence,is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₁, ateach occurrence, is independently selected from alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(11a); R_(11a), at eachoccurrence, is independently selected from alkyl, haloalkyl, aryl,alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉, —S(O)₂NR₁₄C(═O)NR₁₄R₁₄,—C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄,—C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₂, at each occurrence, isindependently selected from hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(10a); R₁₄, at eachoccurrence, is independently selected from hydrogen, alkyl, cycloalkyland aryl; and R₂₀ and R₂₁ are each independently selected from the groupconsisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and—OC(═O)R₁₀.
 5. A compound according to claim 1 selected from the groupconsisting of compounds of Formula I and IA wherein: ring A isoptionally substituted with one or more R's shown as R₂₀ and R_(2i); Gis CH or N; Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂; n₁ is0-2; n₂ is 0-2; n₃ is 1-2; R₁ is a 6-membered monocyclic aryl, a5-membered monocyclic heteroaryl or a 6-membered monocyclic heteroaryl,each of which may be optionally substituted with one or more membersselected from R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e); R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e) are each independently selected from the groupconsisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl,heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₁,—OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉, —S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉,—C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) the alkenyl, alkynyl,cycloalkyl, aryl and heterocyclyl may each be optionally substitutedwith one or more R₆'s; and (b) the alkyl may optionally be substitutedby one or more of R₇'s; R₂ is heteroaryl or —C(═O)OR₅, wherein theheteroaryl may be optionally substituted with one or more R₆'s; R₃ ishydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl or heterocyclylalkyl; R₅ is alkyl,alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, each of which maybe optionally substituted with one or more R₆'s; R₆, at each occurrence,is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₀, —OCF₃,—OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₉R₉, —NR₉R₉,—S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉, —S(O)₂NR₉C(═O)OR₉,—S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H,—NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀,—S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl,alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl may each be optionally substitutedwith 0-5 R_(9a); R₇, at each occurrence, is independently selected fromthe group consisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a); R₈, at each occurrence, is independently selected from thegroup consisting of alkyl, aryl, cycloalkyl, heteroaryl andheterocyclyl, each of which may be optionally substituted with one ormore R_(8a)'s; R_(8a), at each occurrence, is independently selectedfrom alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃,—OR₁₄; —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄;—S(O)₂NR₁₄C(═O)NR₁₄R₁₄; —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄; —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄; R₉, at eachoccurrence, is independently selected from hydrogen, alkyl, alkoxy,cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyland heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may eachbe optionally substituted with 0-5 R_(9a); R_(9a), at each occurrence,is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄; —OCF₃,—OR₁₄; —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄; —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀;—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄;—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₁, ateach occurrence, is independently selected from alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(11a); R_(11a), at eachoccurrence, is independently selected from alkyl, haloalkyl, aryl,alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉, —S(O)₂NR₁₄C(═O)NR₁₄R₁₄,—C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄,—C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₂, at each occurrence, isindependently selected from hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(10a); R₁₄, at eachoccurrence, is independently selected from hydrogen, alkyl, cycloalkyland aryl; and R₂₀ and R₂₁ are each independently selected from the groupconsisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and—OC(═O)R₁₀.
 6. A compound according to claim 1 selected from the groupconsisting of compounds of Formula I and Formula IA wherein: ring A isoptionally substituted with one or more R's shown as R₂₀ and R_(2i); Gis CH or N; Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O) or S(O)₂; n₁ is0-2; n₂ is 0-2; n₃ is 1-2; R₁ is a 6-membered monocyclic aryl, a5-membered monocyclic heteroaryl or a 6-membered monocyclic heteroaryl,each of which may be optionally substituted with one or more membersselected from R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e); R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e) are each independently selected from the groupconsisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl,heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₁,—OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉,—NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉, —S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉,—C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀,—OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) the alkenyl, alkynyl,cycloalkyl, aryl and heterocyclyl may each be optionally substitutedwith one or more R₆'s; and (b) the alkyl may optionally be substitutedby one or more of VS; R₂ is heteroaryl which may be optionallysubstituted with one or more R₆'s; R₃ is hydrogen, alkyl, alkoxy,cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclylor heterocyclylalkyl; R₆, at each occurrence, is independently selectedfrom alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₀, —OCF₃,—OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₉R₉, —NR₉R₉,—S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉, —S(O)₂NR₉C(═O)OR₉,—S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H,—NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀,—S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl,alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl may each be optionally substitutedwith 0-5 R_(9a); R₇, at each occurrence, is independently selected fromthe group consisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a); R₈, at each occurrence, is independently selected from thegroup consisting of alkyl, aryl, cycloalkyl, heteroaryl andheterocyclyl, each of which may be optionally substituted with one ormore R_(8a)'s; R_(8a), at each occurrence, is independently selectedfrom alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄; R₉, at eachoccurrence, is independently selected from hydrogen, alkyl, alkoxy,cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyland heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may eachbe optionally substituted with 0-5 R_(9a); R_(9a), at each occurrence,is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₁, ateach occurrence, is independently selected from alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(11a); R_(11a), at eachoccurrence, is independently selected from alkyl, haloalkyl, aryl,alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉, —S(O)₂NR₁₄C(═O)NR₁₄R₁₄,—C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄,—C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₂, at each occurrence, isindependently selected from hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(10a); R₁₄, at eachoccurrence, is independently selected from hydrogen, alkyl, cycloalkyland aryl; and R₂₀ and R₂₁ are each independently selected from the groupconsisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and—OC(═O)R₁₀.
 7. A compound according to claim 1 selected from compoundsof Formula IA wherein: ring A is optionally substituted with one or moreR's shown as R₂₀ and R₂₁; G is CH or N; Y is CH₂, N(R₃), C(═O), O,OCR₉R₉, S, S(═O) or S(O)₂; n₁ is 0-2; n₂ is 0-2; R₁ is a 6-memberedmonocyclic aryl, a 5-membered monocyclic heteroaryl or a 6-memberedmonocyclic heteroaryl, each of which may be optionally substituted withone or more members selected from R_(1a), R_(1b), R_(1c), R_(1d) andR_(1e); R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e) are each independentlyselected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s; R₂ is cycloalkyl,aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅, —C(═O)R₅ or—C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; R₃ is hydrogen,alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl or heterocyclylalkyl; R₅ is alkyl, alkenyl, aryl,cycloalkyl, heteroaryl or heterocyclyl, each of which may be optionallysubstituted with one or more R₆'s; R₆, at each occurrence, isindependently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₀, —OCF₃,—OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₉R₉, —NR₉R₉,—S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉, —S(O)₂NR₉C(═O)OR₉,—S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H,—NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀,—S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl,alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl may each be optionally substitutedwith 0-5 R_(9a); R₇, at each occurrence, is independently selected fromthe group consisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a); R₈, at each occurrence, is independently selected from thegroup consisting of alkyl, aryl, cycloalkyl, heteroaryl andheterocyclyl, each of which may be optionally substituted with one ormore R_(8a)'s; R_(8a), at each occurrence, is independently selectedfrom alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄; R₉, at eachoccurrence, is independently selected from hydrogen, alkyl, alkoxy,cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyland heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may eachbe optionally substituted with 0-5 R_(9a); R_(9a), at each occurrence,is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₁, ateach occurrence, is independently selected from alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(11a); R_(11a), at eachoccurrence, is independently selected from alkyl, haloalkyl, aryl,alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉, —S(O)₂NR₁₄C(═O)NR₁₄R₁₄,—C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄,—C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄; —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₂, at each occurrence, isindependently selected from hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(10a); R₁₄, at eachoccurrence, is independently selected from hydrogen, alkyl, cycloalkyland aryl; R₂₀ is hydrogen; and R₂₁ is selected from the group consistingof hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀. 8.A compound according to claim 1 selected from compounds of Formula Iwherein: ring A is optionally substituted with one or more R's shown asR₂₀ and R₂₁; G is CH or N; Y is CH₂, N(R₃), C(═O), O, OCR₉R₉, S, S(═O)or S(O)₂; n₁ is 0-2; n₂ is 0-2; n₃ is 2; R₁ is a 6-membered monocyclicaryl, a 5-membered monocyclic heteroaryl or a 6-membered monocyclicheteroaryl, each of which may be optionally substituted with one or moremembers selected from R_(1a), R_(1b), R_(1c), R_(1d) and R_(1e); R_(1a),R_(1b), R_(1c), R_(1d) and R_(1e) are each independently selected fromthe group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl,aryl, heterocyclyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₀, —OCF₃,—OR₁₁, —OH, —SH, —SR₁₁, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₉R₉, —NR₁₂R₁₂,—S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉, —S(O)₂NR₉C(═O)OR₉,—S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H,—NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein: (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; and (b) the alkylmay optionally be substituted by one or more of R₇'s; R₂ is cycloalkyl,aryl, heteroaryl, heterocyclyl, —S(O)₂R₅, —C(═O)NR₃R₅, —C(═O)R₅ or—C(═O)OR₅, wherein the cycloalkyl, aryl, heteroaryl and heterocyclyl mayeach be optionally substituted with one or more R₆'s; R₃ is hydrogen,alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl or heterocyclylalkyl; R₅ is alkyl, alkenyl, aryl,cycloalkyl, heteroaryl or heterocyclyl, each of which may be optionallysubstituted with one or more R₆'s; R₆, at each occurrence, isindependently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₀, —OCF₃,—OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₉R₉, —NR₉R₉,—S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉, —S(O)₂NR₉C(═O)OR₉,—S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H,—NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀,—S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein the alkyl, alkenyl,alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl may each be optionally substitutedwith 0-5 R_(9a); R₇, at each occurrence, is independently selected fromthe group consisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heterocyclyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₉R₉, —NR₉R₉, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)NR₉S(O)₂R₉,—S(O)₂NR₉C(═O)OR₉, —S(O)₂NR₉C(═O)NR₉R₉, —C(═O)NR₉S(O)₂CF₃, —C(═O)R₁₀,—NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —C(═NR₁₄)NR₉R₉,—NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and—NR₉S(O₂)R₈, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl,cycloalkylalkyl and heterocyclyl may each be optionally substituted with0-5 R_(9a); R₈, at each occurrence, is independently selected from thegroup consisting of alkyl, aryl, cycloalkyl, heteroaryl andheterocyclyl, each of which may be optionally substituted with one ormore R_(8a)'s; R_(8a), at each occurrence, is independently selectedfrom alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl,cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₄, —S(O)₂NR₁₄C(═O)OR₁₄,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄; R₉, at eachoccurrence, is independently selected from hydrogen, alkyl, alkoxy,cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyland heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may eachbe optionally substituted with 0-5 R_(9a); R_(9a), at each occurrence,is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,heterocyclylalkyl, halo, —NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃,—OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₁₀, —S(O)₂NR₁₄C(═O)OR₁₀,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈, ═O and arylalkyl;R₁₀, at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl may each be optionally substituted with 0-3 R_(10a);R_(10a), at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo,—NH₂, —CN, —NO₂, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄,—S(O)₃H, —P(O)₃H₂, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉,—S(O)₂NR₁₄C(═O)NR₁₄R₁₄, —C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H,—NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₁, ateach occurrence, is independently selected from alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(11a); R_(11a), at eachoccurrence, is independently selected from alkyl, haloalkyl, aryl,alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH₂, —CN, —NO₂,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —SH, —SR₁₄, —S(O)₃H, —P(O)₃H₂,—C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃,—C(═O)NR₁₄S(O)₂R₉, —S(O)₂NR₁₄C(═O)OR₉, —S(O)₂NR₁₄C(═O)NR₁₄R₁₄,—C(═O)NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄,—C(═NR₁₄)NR₁₄R₁₄, —NHC(═NR₁₄)NR₁₄R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and arylalkyl; R₁₂, at each occurrence, isindependently selected from hydrogen, alkyl, alkenyl, alkynyl,cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, whereinthe cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl mayeach be optionally substituted with 0-3 R_(10a); R₁₄, at eachoccurrence, is independently selected from hydrogen, alkyl, cycloalkyland aryl; R₂₀ is hydrogen; and R₂₁ is selected from the group consistingof hydrogen, alkyl, haloalkyl, cycloalkyl, halo, —CN, —C(═O)OH,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀. 9.A compound according to claim 1 selected from compounds of Formula IAwherein: ring A is optionally substituted with one or more R's shown asR₂₀ and R₂₁; G is CH or N; Y is O, OCR₉R₉, or S; n₁ is 1; n₂ is 1; R₁ isphenyl or a 6-membered monocyclic heteroaryl, each of which may beoptionally substituted with one or more members selected from R_(1a),R_(1b), R_(1c), R_(1d) and R_(1e); R_(1a), R_(1b), R_(1d) and R_(1e) areeach independently selected from the group consisting of hydrogen,alkyl, alkenyl, alkynyl, cycloalkyl, halo, —CN, —OCF₃, —OR₁₁, —OH,—C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H,—NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) the alkenyl, alkynyl andcycloalkyl may each be optionally substituted with one or more R₆'s; and(b) the alkyl may optionally be substituted by one or more of R₇'s;R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s; R₂ is heteroaryl or—C(═O)OR₅, wherein the heteroaryl may be optionally substituted with oneor more R₆'s; R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl orheterocyclyl, each of which may be optionally substituted with one ormore R₆'s; R₆, at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉,—S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀,—OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may eachbe optionally substituted with 0-5 R_(9a); R₇, at each occurrence, isindependently selected from the group consisting of alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, halo,—CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉,—S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀,—OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyland heterocyclyl may each be optionally substituted with 0-5 R_(9a); R₈,at each occurrence, is independently selected from the group consistingof alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, each of whichmay be optionally substituted with one or more R_(8a)'s; R_(8a), at eachoccurrence, is independently selected from alkyl, haloalkyl, aryl,alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN, —C(═O)OH, —C(═O)OR₁₄,—OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄; R₉, at eachoccurrence, is independently selected from hydrogen, alkyl, alkoxy,cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyland heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may eachbe optionally substituted with 0-5 R_(9a); R_(9a), at each occurrence,is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, halo, —NH₂, —CN, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH,—C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄,—NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O; R₁₀, at each occurrence, isindependently selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-3 R_(10a); R_(10a), at each occurrence, isindependently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈; R₁₁,at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a); R_(11a), at each occurrence, is independently selected fromalkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈; R₁₂,at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a); R₁₀, at each occurrence, is independently selected fromhydrogen, alkyl, cycloalkyl and aryl; R₂₀ is hydrogen; and R₂₁ isselected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.
 10. A compound according to claim1 selected from compounds of Formula I wherein: ring A is optionallysubstituted with one or more R's shown as R₂₀ and R₂₁; G is CH or N; Yis O, OCR₉R₉, or S; n₁ is 1; n₂ is 1; n₃ is 2; R₁ is phenyl or a6-membered monocyclic heteroaryl, each of which may be optionallysubstituted with one or more members selected from R_(1a), R_(1b),R_(1c), R_(1d) and R_(1e); R_(1a), R_(1b), R_(1d) and R_(1e) are eachindependently selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, halo, —CN, —OCF₃, —OR₁₁, —OH, —C(═O)NR₉R₉,—NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₁, —NR₉C(═O)H,—NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉, —S(═O)R₁₁, —S(O)₂R₁₁,—NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) the alkenyl, alkynyl andcycloalkyl may each be optionally substituted with one or more R₆'s; and(b) the alkyl may optionally be substituted by one or more of R₇'s;R_(1c) is selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —CN, —OCF₃,—OR₁₁, —OH, —SR₁₁, —C(═O)NR₉R₉, —NR₁₂R₁₂, —S(O)₂NR₉R₉, —NR₉S(O)₂CF₃,—C(═O)R₁₁, —NR₉C(═O)H, —NR₉C(═O)R₁₀, —OC(═O)R₁₀, —OC(═O)NR₉R₉,—S(═O)R₁₁, —S(O)₂R₁₁, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈, wherein: (a) thealkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each beoptionally substituted with one or more R₆'s; and (b) the alkyl mayoptionally be substituted by one or more of R₇'s; R₂ is heteroaryl or—C(═O)OR₅, wherein the heteroaryl may be optionally substituted with oneor more R₆'s; R₅ is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl orheterocyclyl, each of which may be optionally substituted with one ormore R₆'s; R₆, at each occurrence, is independently selected from alkyl,haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —CN,—C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉,—S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀,—OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may eachbe optionally substituted with 0-5 R_(9a); R₇, at each occurrence, isindependently selected from the group consisting of alkyl, haloalkyl,aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, halo,—CN, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH, —SH, —SR₁₀, —C(═O)NR₉R₉, —NR₉R₉,—S(O)₂NR₉R₉, —NR₉S(O)₂CF₃, —C(═O)R₁₀, —NR₉C(═O)H, —NR₉C(═O)R₁₀,—OC(═O)R₁₀, —S(═O)R₁₀, —S(O)₂R₁₀, ═O, —NR₉C(═O)OR₈ and —NR₉S(O₂)R₈,wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyland heterocyclyl may each be optionally substituted with 0-5 R₉₉; R₈, ateach occurrence, is independently selected from the group consisting ofalkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, each of which maybe optionally substituted with one or more R_(8a)'s; R_(8a), at eachoccurrence, is independently selected from alkyl, haloalkyl, aryl,alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN, —C(═O)OH, —C(═O)OR₁₄,—OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄,—NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄,—S(═O)R₁₄, —S(O)₂R₁₄, ═O, —NR₁₄C(═O)OR₁₄ and —NR₁₄S(O₂)R₁₄; R₉, at eachoccurrence, is independently selected from hydrogen, alkyl, alkoxy,cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyland heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl,heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may eachbe optionally substituted with 0-5 R_(9a); R_(9a), at each occurrence,is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,cycloalkyl, halo, —NH₂, —CN, —C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH,—C(═O)NR₁₄R₁₄, —NR₁₄R₁₄, —S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄,—NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄, —OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄,—NR₁₄C(═O)OR₈, —NR₁₄S(O₂)R₈ and ═O; R₁₀, at each occurrence, isindependently selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl,arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heteroaryl,heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each beoptionally substituted with 0-3 R_(10a); R_(10a), at each occurrence, isindependently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl,halo, —NH₂, —CN, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈; R₁₁,at each occurrence, is independently selected from alkyl, alkenyl,alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(11a); R_(11a), at each occurrence, is independently selected fromalkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, halo, —NH₂, —CN,—C(═O)OH, —C(═O)OR₁₄, —OCF₃, —OR₁₄, —OH, —C(═O)NR₁₄R₁₄, —NR₁₄R₁₄,—S(O)₂NR₁₄R₁₄, —NR₁₄S(O)₂CF₃, —C(═O)R₁₄, —NR₁₄C(═O)H, —NR₁₄C(═O)R₁₄,—OC(═O)R₁₄, —S(═O)R₁₄, —S(O)₂R₁₄, —NR₁₄C(═O)OR₈ and —NR₁₄S(O₂)R₈; R₁₂,at each occurrence, is independently selected from hydrogen, alkyl,alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl andheterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyland heterocyclylalkyl may each be optionally substituted with 0-3R_(10a); R₁₄, at each occurrence, is independently selected fromhydrogen, alkyl, cycloalkyl and aryl; R₂₀ is hydrogen; and R₂₁ isselected from the group consisting of hydrogen, alkyl, haloalkyl,cycloalkyl, halo, —CN, —C(═O)OH, —C(═O)OR₁₀, —OCF₃, —OR₁₀, —OH,—C(═O)NR₉R₉, —C(═O)R₁₀ and —OC(═O)R₁₀.
 11. A compound of the formula


12. A pharmaceutical composition comprised of a therapeuticallyeffective amount of a compound of claim 1 and, optionally, apharmaceutically acceptable carrier.
 13. The pharmaceutical compositionof claim 12 further comprising one or more other therapeutically activeagents.
 14. A method of modulating the activity of the GPR119 Gprotein-coupled receptor comprising administering to a mammalian patientin need thereof a therapeutically effective amount of at least onecompound of claim 1 and, optionally, an additional therapeutic agent.15. A method for preventing, inhibiting, or treating the progression oronset of diseases or disorders associated with the activity of theGPR119 G protein-coupled receptor comprising administering to amammalian patient in need of prevention, inhibition, or treatment atherapeutically effective amount of at least one compound of claim 1and, optionally, an additional therapeutic agent wherein: (a) thediseases or disorders are selected from the group consisting ofdiabetes, hyperglycemia, impaired glucose tolerance, insulin resistance,hyperinsulinemia, retinopathy, neuropathy, nephropathy, delayed woundhealing, atherosclerosis and its sequelae, abnormal heart function,myocardial ischemia, stroke, Metabolic Syndrome, hypertension, obesity,dislipidemia, dyslipidemia, hyperlipidemia, hypertriglyceridemia,hypercholesterolemia, low HDL, high LDL, non-cardiac ischemia,infection, cancer, vascular restenosis, pancreatitis, neurodegenerativedisease, lipid disorders, cognitive impairment and dementia, bonedisease, HIV protease associated lipodystrophy and glaucoma; and (b) theadditional therapeutic agent is selected from the group consisting ofanti-diabetic agents, anti-hyperglycemic agents, anti-hyperinsulinemicagents, anti-retinopathic agents, anti-neuropathic agents,anti-nephropathic agents, anti-atherosclerotic agents, anti-ischemicagents, anti-hypertensive agents, anti-obesity agents, anti-dyslipidemicagents, anti-dyslipidemic agents, anti-hyperlipidemic agents,anti-hypertriglyceridemic agents, anti-hypercholesterolemic agents,anti-restenotic agents, anti-pancreatic agents, lipid lowering agents,appetite suppressants, treatments for heart failure, treatments forperipheral arterial disease and anti-inflammatory agents.
 16. Apharmaceutical composition comprising a therapeutically effective amountof a compound of claim 1 and a therapeutically effective amount of adipeptidyl peptidase-IV (DPP4) inhibitor.